Language：English   Publishing type：Research paper (scientific journal)  

Under normal conditions, fasting results in decreased protein disulfide isomerase (PDI) activity and accumulation of unfolded proteins, leading to the subsequent activation of the unfolded protein response (UPR)/autophagy signaling pathway to eliminate damaged mitochondria. Fasting also induces upregulation of thioredoxin-interacting protein (TXNIP) expression and mice deficient of this protein (TXNIP-KO mice) was shown to develop severe hypoglycemia, hyperlipidemia and liver steatosis (LS). In the present study, we aimed to determine the role of TXNIP in fasting-induced LS by using male TXNIP-KO mice that developed LS without severe hypoglycemia. In TXNIP-KO mice, fasting induced severe microvesicular LS. Examinations by transmission electron microscopy revealed mitochondria with smaller size and deformities and the presence of few autophagosomes. The expression of β-oxidation-associated genes remained at the same level and the level of LC3-II was low. PDI activity level stayed at the original level and the levels of p-IRE1 and X-box binding protein 1 spliced form (sXBP1) were lower. Interestingly, treatment of TXNIP-KO mice with bacitracin, a PDI inhibitor, restored the level of LC3-II after fasting. These results suggest that TXNIP regulates PDI activity and subsequent activation of the UPR/autophagy pathway and plays a protective role in fasting-induced LS.

DOI： 10.1038/s41598-022-08791-z

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japanese Society for Pediatric Endocrinology  

Rathke's cleft cysts (RCCs) are non-neoplastic epithelial lesions in the sellar or suprasellar regions. RCCs are usually asymptomatic; however, some patients experience headaches, visual disturbances, and endocrine disorders. The best treatment for associated endocrinopathy remains elusive. We aimed to investigate the clinical course, magnetic resonance imaging findings, and response to therapy in 10 pediatric patients with RCCs and endocrinopathy. Growth impairment and precocious puberty were observed to be prevalent. One patient with suprasellar extension of RCC underwent surgery, while the others were treated medically. Of the nine patients, seven patients showed stable cyst size, while two patients displayed reduction in cyst size. Hormone replacement and gonadotropin suppression therapy were found to be effective. Imaging and endocrine follow-ups are warranted because of the potential for changes in the cyst size and hormonal changes.

DOI： 10.1297/cpe.2021-0034

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japanese Society for Pediatric Endocrinology  

DOI： 10.1297/cpe.2021-0036

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

Pathogenic-activating variants of interferon induced with Helicase C domain 1 (IFIH1) cause Singleton-Merten (S-M) syndrome, which accompanies acro-osteolysis, loss of permanent teeth, and aortic calcification, as well as causing Aicardi-Goutières (A-G) syndrome, which shows progressive encephalopathy, spastic paraplegia, and calcification of basal ganglia. Recently, patients with overlapping syndromes presenting with features of S-M syndrome and A-G syndrome were reported. However, progression of clinical features of this condition has not been fully understood. We report a Japanese boy with a novel pathogenic IFIH1 variant who presented with clinical features of S-M syndrome and A-G syndrome.

DOI： 10.1002/ajmg.a.62478

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Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/ajmg.a.62478

Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Osteogenesis imperfecta (OI) is a rare connective-tissue disorder characterized by bone fragility. Approximately 90% of all OI cases are caused by variants in COL1A1 or COL1A2. Additionally, IFITM5 variants are responsible for the unique OI type 5. We previously analyzed COL1A1/2 variants in 22 Japanese families with OI through denaturing high-performance liquid chromatography screening, but our detection rate was low (41%). METHODS: To expand the genotype-phenotype correlations, we performed a genetic analysis of COL1A1/2 and IFITM5 in 96 non-consanguineous Japanese OI probands by Sanger sequencing. RESULTS: Of these individuals, 54, 41, and 1 had type 1 (mild), type 2-4 (moderate-to-severe), and type 5 phenotypes, respectively. In the mild group, COL1A1 nonsense and splice-site variants were prevalent (n = 30 and 20, respectively), but there were also COL1A1 and COL1A2 triple-helical glycine substitutions (n = 2 and 1, respectively). In the moderate-to-severe group, although COL1A1 and COL1A2 glycine substitutions were common (n = 14 and 18, respectively), other variants were also detected. The single case of type 5 had the characteristic c.-14C>T variant in IFITM5. CONCLUSION: These results increase our previous detection rate for COL1A1/2 variants to 99% and provide insight into the genotype-phenotype correlations in OI.

DOI： 10.1002/mgg3.1675

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier {BV}  

BACKGROUND: We aimed to demonstrate the biochemical characteristics of vitamin B6-dependent epilepsy, with a particular focus on pyridoxal 5'-phosphate and pyridoxal in the cerebrospinal fluid. METHODS: Using our laboratory database, we identified patients with vitamin B6-dependent epilepsy and extracted their data on the concentrations of pyridoxal 5'-phosphate, pyridoxal, pipecolic acid, α-aminoadipic semialdehyde, and monoamine neurotransmitters. We compared the biochemical characteristics of these patients with those of other epilepsy patients with low pyridoxal 5'-phosphate concentrations. RESULTS: We identified seven patients with pyridoxine-dependent epilepsy caused by an ALDH7A1 gene abnormality, two patients with pyridoxal 5'-phosphate homeostasis protein deficiency, and 28 patients with other epilepsies with low cerebrospinal fluid pyridoxal 5'-phosphate concentrations. Cerebrospinal fluid pyridoxal and pyridoxal 5'-phosphate concentrations were low in patients with vitamin B6-dependent epilepsy but cerebrospinal fluid pyridoxal concentrations were not reduced in most patients with other epilepsies with low cerebrospinal fluid pyridoxal 5'-phosphate concentrations. Increase in 3-O-methyldopa and 5-hydroxytryptophan was demonstrated in some patients with vitamin B6-dependent epilepsy, suggestive of pyridoxal 5'-phosphate deficiency in the brain. CONCLUSIONS: Low cerebrospinal fluid pyridoxal concentrations may be a better indicator of pyridoxal 5'-phosphate deficiency in the brain in vitamin B6-dependent epilepsy than low cerebrospinal fluid pyridoxal 5'-phosphate concentrations. This finding is especially helpful in individuals with suspected pyridoxal 5'-phosphate homeostasis protein deficiency, which does not have known biomarkers.

DOI： 10.1016/j.pediatrneurol.2020.08.020

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BACKGROUND: Renal calcified lesions are known as one of the complications during adrenocorticotropic hormone (ACTH) therapy for intractable epilepsy. However, laboratory changes during the therapy or laboratory features of high-risk cases with renal calcified lesions are yet to be clarified. METHODS: In this study, 43 patients with West syndrome aged ≤2 years were included. We retrospectively reviewed age and body mass index at the beginning of ACTH therapy, as well as the amount of fluid intake, daily urinary volume, and laboratory data during therapy. In addition, we studied the urinary sediment of the cases with renal calcified lesions diagnosed by computed tomography. RESULTS: After initiating ACTH treatment, urinary calcium (Ca)/creatinine ratio and urinary pH increased within 2 weeks. Urinary crystals and renal tubular epithelial cells (RTECs) in urinary sediment were frequently found in most cases. Urinary Ca levels, proteinuria or frequency of urinary crystals, and number of RTECs in the urinary sediment were significantly higher in patients with epithelial casts (ECs) or hematuria than in patients without these findings. Among the seven patients who underwent abdominal CT, ECs or hematuria were found only in those with renal calcified lesions. These findings suggested that patients with ECs or hematuria were more likely to have calcified lesions. CONCLUSIONS: The risk of renal calcified lesions increased after 2 weeks of ACTH treatment. Abnormal findings in urinary sediments might be an early sign of renal calcification during ACTH therapy.

DOI： 10.1111/ped.14158

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<jats:title>Abstract</jats:title>
<jats:p>Pyridoxine-dependent epilepsy (PDE) is a rare autosomal-recessive disorder typically presenting with neonatal seizures and is sometimes difficult to diagnose, because the clinical features mimic those of birth asphyxia. A Japanese newborn boy presented with pulmonary haemorrhage and convulsions on the day of birth. Brain computed tomography showed diffuse, but mild, low-density cerebral white matter and a thin subdural hematoma in the posterior fossa. He did not have thrombocytopenia or coagulopathy. His respiratory status improved with conservative treatment, but his convulsions were persistent even after prescription of several antiepileptic drugs. His serum and cerebrospinal fluid showed decreased vitamin B6 vitamers and increased upstream metabolites of α-aminoadipic semialdehyde dehydrogenase, strongly suggesting a diagnosis of PDE; the epileptic spasms ceased after administration of intravenous pyridoxal phosphate hydrate. Gene analysis revealed novel compound heterozygous mutations in ALDH7A1 that included NM_001182.4:[c.1196G &amp;gt; T] and [c.1200 + 1G &amp;gt; A]. Atypical birth asphyxia with persistent neonatal seizure should prompt vitamin B6/metabolite screening.</jats:p>

DOI： 10.1093/omcr/omaa008

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Achondroplasia (ACH) is a skeletal dysplasia that presents with limb shortening, short stature, and characteristic facial configuration. ACH is caused by mutations of the FGFR3 gene, leading to constantly activated FGFR3 and activation of its downstream intracellular signaling pathway. This results in the suppression of chondrocyte differentiation and proliferation, which in turn impairs endochondral ossification and causes short-limb short stature. ACH also causes characteristic clinical symptoms, including foramen magnum narrowing, ventricular enlargement, sleep apnea, upper airway stenosis, otitis media, a narrow thorax, spinal canal stenosis, spinal kyphosis, and deformities of the lower extremities. Although outside Japan, papers on health supervision are available, they are based on reports and questionnaire survey results. Considering the scarcity of high levels of evidence and clinical guidelines for patients with ACH, clinical practical guidelines have been developed to assist both healthcare professionals and patients in making appropriate decisions in specific clinical situations. Eleven clinical questions were established and a systematic literature search was conducted using PubMed/MEDLINE. Evidence-based recommendations were developed, and the guidelines describe the recommendations related to the clinical management of ACH. We anticipate that these clinical practice guidelines for ACH will be useful for healthcare professionals and patients alike.

DOI： 10.1297/cpe.29.25

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Hypophosphatasia (HPP) is a rare bone disease caused by inactivating mutations in the ALPL gene, which encodes tissue-nonspecific alkaline phosphatase (TNSALP). Patients with HPP have varied clinical manifestations and are classified based on the age of onset and severity. Recently, enzyme replacement therapy using bone-targeted recombinant alkaline phosphatase (ALP) has been developed, leading to improvement in the prognosis of patients with life-threatening HPP. Considering these recent advances, clinical practice guidelines have been generated to provide physicians with guides for standard medical care for HPP and to support their clinical decisions. A task force was convened for this purpose, and twenty-one clinical questions (CQs) were formulated, addressing the issues of clinical manifestations and diagnosis (7 CQs) and those of management and treatment (14 CQs). A systematic literature search was conducted using PubMed/MEDLINE, and evidence-based recommendations were developed. The guidelines have been modified according to the evaluations and suggestions from the Clinical Guideline Committee of The Japanese Society for Pediatric Endocrinology (JSPE) and public comments obtained from the members of the JSPE and a Japanese HPP patient group, and then approved by the Board of Councils of the JSPE. We anticipate that the guidelines will be revised regularly and updated.

DOI： 10.1297/cpe.29.9

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Nager syndrome is a rare disease involving severe micrognathia and upper limb shortening. In this report, we describe a case in which micrognathia of the fetus was suspected based on the observation of upper limb shortening during detailed B mode and 3D/4D ultrasonographic observation, and combined fetal MRI and 3D-CT led to a prenatal diagnosis of Nager syndrome. Upon birth, because severe micrognathia caused airway obstruction and made it difficult to spread the larynx for intubation, effective ventilation could not be carried out and a tracheostomy was necessary. Since a differential diagnosis of Nager syndrome can be made based on the fact that micrognathia typically co-occurs with upper limb shortening, it is possible to diagnose the disease before birth and prepare for life-saving measures accordingly.

DOI： 10.18926/AMO/56872

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1297/cpe.28.155

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We studied the etiology of pediatric acute encephalitis/encephalopathy (pAEE) using epidemiological data obtained from a nationwide survey in Japan. Two-step questionnaires were sent to the pediatric departments of hospitals throughout the country in 2007, querying the number of the cases during 2005-2006 as the first step, and asking for the details of clinical information as the second step. In all, 636 children with pAEE (age ≤ 15 years) were enrolled. For the known etiology of pAEE (63.5% of the total cases), 26 microbes and 2 clinical entities were listed, but the etiology of 36.5% remained unknown. Influenza virus (26.7%), exanthem subitum (12.3%), and rotavirus (4.1%) were the most common, and the incidence of pAEE peaked at the age of 1 year. This trend was common among all etiologies. Among the neurological symptoms observed at the onset of pAEE, seizures were observed more often in patients aged ≤ 3 years, although abnormal speech and behavior were also common in older children. Undesirable outcomes (death and neurological sequelae) occurred at high rates in patients with any known etiology other than mycoplasma. In conclusion, these findings provide comprehensive insight into pAEE in Japan.

DOI： 10.18926/AMO/56170

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There is concern that vitamin D deficiency is prevalent among children in Japan as well as worldwide. We conducted a nationwide epidemiologic survey of symptomatic vitamin D deficiency to observe its incidence rate among Japanese children. A questionnaire inquiring the number of new patients with vitamin D deficiency rickets and/or hypocalcemia for 3 years was sent to 855 randomly selected hospitals with a pediatrics department in Japan. In this survey, we found that 250 children were diagnosed with symptomatic vitamin D deficiency. The estimated number of patients with symptomatic vitamin D deficiency per year was 183 (95% confidence interval (CI): 145-222). The overall annual incidence rate among children under 15 years of age was 1.1 per 100,000 population (95% CI: 0.9-1.4). The second survey has provided detailed information on 89 patients with symptomatic vitamin D deficiency under 5 years of age in hospitals in the current research group. The nationwide and second surveys estimated the overall annual incidence rate of symptomatic vitamin D deficiency in children under 5 years of age to be 3.5 (2.7-4.2) per 100,000 population. The second survey revealed 83% had bowed legs, 88% had exclusive breastfeeding, 49% had a restricted and/or unbalanced diet and 31% had insufficient sun exposure among the 89 patients. This is the first nationwide survey on definitive clinical vitamin D deficiency in children in Japan. Elucidating the frequency and characteristics of symptomatic vitamin D deficiency among children is useful to develop preventative public health strategies.

DOI： 10.1507/endocrj.EJ18-0008

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

Patients with 22q11.2 deletion syndrome have characteristic facial appearance, palate abnormalities, hypoparathyroidism, thymic hypoplasia, and congenital heart disease. The 22q11.2 region includes TBX1 and 30 other genes. Analysis of Tbx1 transgenic mice showed that TBX1 was associated with the 22q11.2 deletion syndrome. In humans, TBX1 mutations have been reported in 22q11.2 deletion-negative patients with velocardiofacial syndrome or DiGeorge syndrome. Genotype-phenotype correlations are not fully understood in these patients. We report the case of an infant with a novel heterozygous TBX1 mutation who experienced hypocalcemic seizures. This patient had no palate abnormalities, cardiac anomalies, or the typical facial appearance observed in 22q11.2 deletion syndrome. The presence of thymic hypoplasia prompted us to perform G-banding, fluorescent in situ hybridization, and subsequent TBX1 analysis. We emphasize the importance of diagnosing thymic hypoplasia in hypocalcemic infants without 22q11.2 deletion for detecting TBX1 mutations.

DOI： 10.1297/cpe.27.159

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：BioMed Central Ltd.  

BACKGROUND: Stickler syndrome is a group of collagenopathies characterized by ophthalmic, skeletal, and orofacial abnormalities, with the degree of symptoms varying among patients. Mutations in the COL2A1, COL11A1, and COL11A2 procollagen genes cause Stickler syndrome. Marshall syndrome, caused by a COL11A1 mutation, has clinical overlap with Stickler syndrome. CASE PRESENTATION: A 2-year-old Japanese boy was presented to our hospital with short stature (79.1 cm, -2.52 standard deviation). His past medical history was significant for soft cleft palate and bilateral cataracts. He had a flat midface, micrognathia, and limitations in bilateral elbow flexion. Radiographs showed mild spondyloepiphyseal dysplasia. Initially, we suspected Marshall syndrome, but no mutation was identified in COL11A1. At 8 years old, his height was 116.2 cm (-1.89 standard deviation), and his orofacial characteristics appeared unremarkable. We analyzed the COL2A1 gene and found a novel heterozygous mutation (c.1142 G > A, p.Gly381Asp). CONCLUSIONS: In this case report, we identify a novel missense mutation in the COL2A1 gene in a patient with Stickler syndrome type 1, and we describe age-related changes in the clinical phenotype with regard to orofacial characteristics and height. Genetic analysis is helpful for the diagnosis of this clinically variable and genetically heterogeneous disorder.

DOI： 10.1186/s13256-017-1396-y

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：WALTER DE GRUYTER GMBH  

Acromicric dysplasia (AD) and geleophysic dysplasia (GD) are rare skeletal dysplasias characterized by short stature, acromelia, joint contracture, hepatomegaly, hoarseness and respiratory distress. Compared with GD, AD presents with milder clinical and radiological features. Radiological findings of AD and GD consist of shortened tubular bones of the hands and feet, and deformed capital femoral epiphyses. The genetic cause of AD and some cases of GD was shown to be mutations in the transforming growth factor (TGF) beta-binding-protein-like domain 5 of the fibrillin 1 gene (FBN1), which is also mutated in Marfan syndrome. In the present study, we report and compare the highly varied clinical and radiological features of three Japanese AD/GD children. Our patients, harboring FBN1 mutations p.Tyr1699Cys, p.Ser1750Arg, and p.Gly1762Ser, shared common clinical symptoms such as severe short stature, acromelia and hepatomegaly. Short tubular bones of hands and deformities of femur heads are common radiological features of our patients.

DOI： 10.1515/jpem-2016-0258

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Jeff Corporation Co. Ltd  

Acanthosis nigricans (AN) is observed in some cases of skeletal dysplasia. However, AN has occasionally been reported in patients with hypochondroplasia (HCH), and a clinical diagnosis is sometimes difficult when its physical and radiological features are mild. Mutations in the gene encoding the fibroblast growth factor receptor 3 (FGFR3) have been identified as the cause of some types of skeletal dysplasia, which is diagnostically useful. Here, we report the case of a 3-yr-old Japanese boy who presented with AN. His height, weight, head circumference, and arm span were 91.7 cm (-1.95 SD), 16.3 kg, 54.0 cm (+2.6 SD), and 88.0 cm, respectively. In addition to the AN, he also exhibited a mild height deficit and macrocephaly, which prompted a search for FGFR3 mutations, although no skeletal disproportion, exaggerated lumbar lordosis, or facial dysmorphism was observed, and only slight radiological abnormalities were noted. A definitive diagnosis of HCH was made based on FGFR3 gene analysis, which detected a heterozygous K650T mutation. Insulin insensitivity was not found to have contributed to the development of AN. In individuals with AN, careful assessments for symptoms of HCH are important, regardless of the presence or absence of a short stature, and FGFR3 gene analysis is recommended in such cases.

DOI： 10.1297/cpe.26.223

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

Genetic mutation of the coproporphyrinogen oxidase (CPOX) gene causes either hereditary coproporphyria (HCP) or harderoporphyria. HCP, a rare hepatic porphyria, causes acute attacks after puberty and rarely accompanies cutaneous symptoms. In contrast, harderoporphyria is an erythropoietic porphyria that represents photosensitivity and hemolytic anemia from the neonatal period. In patients with harderoporphyria, the p.Lys404Glu mutation is found in the homozygous or compound heterozygous state with another mutation, and a marked increase in harderoporphyrin is observed. This report describes a neonate with symptoms of erythropoietic harderoporphyria (photosensitivity of the skin, hemolytic anemia, and jaundice). However, the pattern of porphyrin metabolites of feces was consistent with that of typical HCP, not of harderoporphyria. We found a heterozygous, novel, four-base pair deletion in exon 7 of the CPOX gene, although other mutations including the p.Lys404Glu mutation in CPOX were not found. By unknown etiology, our patient had accompanying adrenocortical insufficiency and 46, XY disorders of sex development. Based on genetic mutation of the CPOX gene and information from a previous similar case report, we consider that neonatal-onset HCP is a variant of HCP.

DOI： 10.1007/8904_2017_20

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：OKAYAMA UNIV MED SCHOOL  

The urinary cross-linked N-terminal telopeptide of type I collagen (uNTx) levels in infantile osteogenesis imperfecta (OI) have not been well studied. Here we investigated the levels of uNTx in infants with OI and healthy infants. We collected spot urine samples from 30 infants with OI (male/female, 14/16; Sillence classification, I/II/III/IV: 15/3/6/6; age, 5.2±4.4 months) and 120 healthy infants (male/female, 75/45; age, 5.1±4.1 months) for the measurement of uNTx levels. The uNTx levels of the OI infants were significantly lower than those of the healthy infants (mean±SD, 1,363.7±530.1 vs. 2,622.2±1,202.6 nmol BCE/mmol Cr; p＜0.001). The uNTx levels of the infants with type I OI were significantly lower than those of the age-matched healthy infants, although an overlap was observed between the 2 groups. Among the 1-month-old infants, the uNTx levels of the infants with types I, III or IV OI were significantly lower than those of the healthy infants, without overlap (1,622.5±235.8 vs. 3,781.0±1,027.1 nmol BCE/mmol Cr; p＜0.001). These results indicate that uNTx levels are significantly lower in infants with OI than in healthy infants, and they suggest that uNTx might be useful as a reference for diagnosing OI.

DOI： 10.18926/AMO/54805

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

DOI： 10.1002/ajmg.a.37557

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：WALTER DE GRUYTER GMBH  

3-M syndrome (OMIM #273750, #612921, and #614205) is a rare autosomal recessive growth disorder that is characterized by pre- and postnatal growth retardation, normal intelligence, and characteristic faces. This syndrome also has characteristic radiological features, such as slender long bones and tall vertebral bodies. Three genes, cullin 7 (CUL7), coiled-coil domain containing 8, and obscurin-like 1 are genetic candidates of 3-M syndrome. Patients with 3-M syndrome have a characteristic facial appearance, including a triangular face, frontal bossing, an anteverted nose, dolichocephaly, and a long philtrum. However, information on adult 3-M syndrome patients, including facial appearance, is scarce. We report an adult female with 3-M syndrome that was caused by novel compound heterozygous mutations (c.4023-1 G>A in splice acceptor site of exon 22 and c.4359_4363dupGGCTG in exon 23) in the CUL7 gene. We also report the growth chart and changes in facial appearance of this patient from the neonate to adult.

DOI： 10.1515/jpem-2015-0272

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：BIOMED CENTRAL LTD  

BACKGROUND: Hypoparathyroidism, sensorineural deafness, and renal dysplasia (HDR) syndrome is an autosomal dominant disorder. We report the first detailed case of hypoparathyroidism complicated by biliary atresia. CASE PRESENTATION: A 1-year-old Japanese girl was admitted to our hospital for living donor liver transplantation. She suffered from obstructive jaundice owing to biliary atresia. She also had persistent hypocalcemia. Despite oral calcium and abundant vitamin D supplementation, a laboratory test showed hypocalcemia (1.4 mmol/l) and hyperphosphatemia (2.6 mmol/l). The intact parathyroid hormone level was normal (66 ng/l) with severe vitamin D deficiency (25-hydroxy vitamin D: undetectable levels). There were no rachitic changes in metaphysis on X-rays. Her family history showed that her mother had sensorineural deafness, a low serum calcium level (2.1 mmol/l), hypoplastic left kidney, and a past history of an operation for right vesicoureteral reflux. We suspected that this patient and her mother have hypoparathyroidism, sensorineural deafness, and renal dysplasia syndrome. A heterozygous GATA3 gene mutation (c.736delGinsAT) was found in this patient and her mother, but not in her father. CONCLUSION: This familial case confirms the importance of family history in the diagnosis of HDR syndrome. Regardless of marked vitamin D deficiency, the complication of hypoparathyroidism prevented the onset of vitamin D deficiency rickets in our patient.

DOI： 10.1186/s12887-016-0550-9

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Jeff Corporation Co. Ltd  

DOI： 10.1297/cpe.24.33

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

Short-limbed short stature is a heterogeneous condition that can result from many diseases such as bone disorder, metabolic disease, and multiple malformation syndrome. We conducted a questionnaire survey of council members of the Japanese Society of Pediatric Endocrinology and doctors of affiliated hospitals in 2010 to investigate short-limbed short stature. Among 91 hospitals, responses were obtained from 61 hospitals (67% response rate). This study also examined data of 193 short-limbed short stature patients, among whom FGFR3-related chondrodysplasia such as achondroplasia (n = 109; 56.5%) was found the most frequently. Second to achondroplasia, hypochondroplasia (n = 47; 24.4%) was the most frequently observed. Along with achondroplasia and hypochondroplasia, 31 patients with disorders of 13 other kinds and six undiagnosed patients were identified. Genetic testing for hypochondroplasia was conducted for only 27.7% of all hypochondroplasia patients, although hypochondroplasia is a heterogeneous condition with many causes, only one of which is FGFR3 mutation. We conducted a genetic analysis of 25 patients who had been clinically diagnosed as having "hypochondroplasia". In these patients, other diseases such as acromicric dysplasia, geleophysic dysplasia, and Aarskog-Scott syndrome were included in addition to FGFR3-related hypochondroplasia (n = 10). Clinical diagnosis of each disorder causing short-limbed short stature is difficult. Therefore, not only clinical diagnosis but also genetic diagnosis play an important role in the diagnosis of short-limb short stature. Diagnostic strategies must be created for each disorder.

DOI： 10.1111/ped.12511

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE INC  

BACKGROUND: Hypophosphatemia and increased serum fibroblast growth factor 23 (FGF23) levels have been reported in young brothers with compound heterozygous mutations for the FAM20C gene; however, rickets was not observed in these cases. We report an adult case of Raine syndrome accompanying hypophosphatemic osteomalacia with a homozygous FAM20C mutation (R408W) associated with increased periosteal bone formation in the long bones and an increase in bone mineral density in the femoral neck. CASE: The patient, a 61-year-old man, was born from a cousin-to-cousin marriage. A short stature and severe dental demineralization were reported at an elementary school age. Hypophosphatemia was noted inadvertently at 27years old, at which time he started to take an active vitamin D metabolite (alphacalcidol) and phosphate. He also manifested ossification of the posterior longitudinal ligament. On bone biopsy performed at the age of 41years, we found severe osteomalacia surrounding osteocytes, which appeared to be an advanced form of periosteocytic hypomineralized lesions compared to those reported in patients with X-linked hypophosphatemic rickets. Laboratory data at 61years of age revealed markedly increased serum intact-FGF23 levels, which were likely to be the cause of hypophosphatemia and the decreased level of 1,25(OH)2D. We recently identified a homozygous FAM20C mutation, which was R408W, in this patient. When expressed in HEK293 cells, the R408W mutant protein exhibited impaired kinase activity and secretion. DISCUSSION: Our findings suggest that certain homozygous FAM20C mutations can cause FGF23-related hypophosphatemic osteomalacia and indicate the multiple roles of FAM20C in bone.

DOI： 10.1016/j.bone.2014.06.026

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Osteogenesis imperfecta (OI) is a condition of decreased bone density with heterogeneous etiologies. Most of the cases are inherited in an autosomal dominant fashion and are caused by mutations in the COL1A1 or COL1A2 genes. Since these two genes are very large, there are no data about mutations in Indian patients with OI. We selected 35 Indian patients who were clinically diagnosed with OI and all exons of both the genes were sequenced. Mutations in COL1A1 (14 cases, 6 novel) and COL1A2 (11 cases, 7 novel) were identified in 25 patients. A total of 55 polymorphisms were identified in both the genes with eight novel variants in the coding region, and nine novel variants in the non-coding regions. No mutation was detected in 10 patients. Six of them were from consanguineous families, with one or two similarly affected siblings suggesting possible autosomal recessive inheritance. If we exclude families with consanguinity, mutations were identified in 25 out of 29 families giving 86% mutation detection rate. Mutations in COL1A1 accounted for 56% of the cases and COL1A2 44%, which is similar to the reported rate worldwide.

DOI： 10.1002/ajmg.a.36481

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JOHN LIBBEY EUROTEXT LTD  

Goltz syndrome or Focal dermal hypoplasia (FDH) is an X-linked dominant disorder characterized by malformations affecting the skin, eyes, central nervous system, and skeletonC:\GetARef\Refs\focal dermal hypoplasia (2007-).re. Mutations in the PORCN gene were identified as the molecular basis of FDH. We report two cases, one caused by a current mutation c.129G&gt;A, which leads to a nonsense mutation W43X, and the other one caused by a novel mutation, c.386delT. The female patient with the recurrent mutation presented with typical cutaneous symptoms and skeletal abnormality, but the female patient with the novel mutation manifested only cutaneous symptoms, with hypo-pigmentation along Blaschko's lines, mainly on her right hemibody. In the latter case, DNA was isolated from peripheral blood cells, lesional skin, and non-lesional skin. The percentage of cells carrying the mutation estimated by subcloning and sequencing of the PCR products was 3.1% in peripheral blood cells, 21% in lesional skin, and 16% in non-lesional skin. X-chromosome inactivation assay showed a slightly skewed pattern in lesional skin, but a random pattern in non-lesional skin and blood. RT-PCR analysis from skin samples showed that PORCN mRNA of the mutated allele had a 13bp nucleotide insertion created by an alternative splicing site. This resulted in abnormal PORCN protein with in-frame insertion of eight amino acids, TTHRGTDD, instead of the original four amino acids, AQMI (126-129). We report a typical FDH patient with a recurrent PORCN mutation, which was previously identified in a male Japanese FDH patient, and a second femal, an almost unilateral FDH patient with a postzygotic PORCN mutation.

DOI： 10.1684/ejd.2012.1911

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE INC  

Fibroblast growth factor 23 (FGF23) is a potent regulator of Pi and 1,25-(OH)(2)D homeostasis. Early postpartum infants show intriguing changes in serum levels of Ca, Pi, PTH and 1,25-(OH)(2)D. However, the role of FGF23 in the early neonatal mineral metabolism has not been clarified. In order to evaluate the significance of FGF23 during the early postpartum period, we examined the circulating FGF23 levels using an intact FGF23 ELISA and a C-terminal FGF23 ELISA either in 22 umbilical cord blood samples (the cord blood) or in 22 term infants at 5days of life (the 5-day-old infant). We also compared these ranges with those of 11 healthy adults. Data were expressed as mean+/-SD, and analyzed by two-way ANOVA, followed by the Tukey's test. C-terminal FGF23 in the cord blood, the 5-day-old infants and the healthy adults were 73.3+/-22.4, 81.0+/-28.2 and 39.0+/-7.8 RU/ml, respectively. Intact FGF23 in the cord blood, the 5-day-old infants and the healthy adults were 3.9+/-1.6, 21.8+/-17.6, and 27.6+/-7.3 pg/ml, respectively. Immunoprecipitation assays using anti-FGF23 antibodies demonstrated that the intact 32 kDa FGF23 was low and the fragmented FGF23 of 18kDa was abundant in the cord blood compared with those in the healthy adults. In conclusion, our observations indicated that the intact FGF23/C-terminal FGF23 ratio was very low due to the fragmentation of FGF23 during the early postpartum period and might have a considerable contribution to the Pi homeostasis in the healthy term infants.

DOI： 10.1016/j.bone.2010.05.024

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

BACKGROUND: Urinary N-telopeptides of type I collagen (NTx) is a specific marker of bone resorption. The NTx levels of children have been reported to be higher than in adults, but such reports are limited. The aim of the present study was to measure the urine NTx of healthy children to define reference values, and study the circadian rhythm of urine NTx excretion between the first and second voided urines. METHODS: Three hundred and sixty-two healthy Japanese children (209 boys and 153 girls; age range, 6-11 years) served as subjects to study age-related changes in NTx. Urine samples were collected as the first voided specimen of the day. To evaluate the circadian variation, we measured the excretion of urinary NTx of the first and second voided urine specimens in 30 healthy Japanese children (15 boys and 15 girls), 6-12 years of age. Urine NTx was measured on enzyme-linked immunosorbent assay (ELISA). RESULTS: Urinary NTx levels were higher in children of both genders than in healthy adults. In boys, the urinary NTx levels decreased with age. In girls, the urinary NTx levels decreased with age between 6 and 9 years of age, but increased between 9 and 10 years of age. NTx of the first voided urine specimen was significantly higher than the second voided urine specimen. Moreover, a significant linear relationship between the first voided urine and the second void urine existed in both genders. CONCLUSIONS: Urinary NTx levels in children are higher than in adults. The urine NTx of the first voided urine specimen may be a good marker of bone resorption for children.

DOI： 10.1111/j.1442-200X.2010.03086.x

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ENDOCRINE SOC  

CONTEXT: Although recent studies have suggested a positive role of OTX2 in pituitary as well as ocular development and function, detailed pituitary phenotypes in OTX2 mutations and OTX2 target genes for pituitary function other than HESX1 and POU1F1 remain to be determined. OBJECTIVE: We aimed to examine such unresolved issues. SUBJECTS: We studied 94 Japanese patients with various ocular or pituitary abnormalities. RESULTS: We identified heterozygous p.K74fsX103 in case 1, p.A72fsX86 in case 2, p.G188X in two unrelated cases (3 and 4), and a 2,860,561-bp microdeletion involving OTX2 in case 5. Clinical studies revealed isolated GH deficiency in cases 1 and 5; combined pituitary hormone deficiency in case 3; abnormal pituitary structures in cases 1, 3, and 5; and apparently normal pituitary function in cases 2 and 4, together with ocular anomalies in cases 1-5. The wild-type Orthodenticle homeobox 2 (OTX2) protein transactivated the GNRH1 promoter as well as the HESX1, POU1F1, and IRBP (interstitial retinoid-binding protein) promoters, whereas the p.K74fsX103-OTX2 and p.A72fsX86-OTX2 proteins had no transactivation functions and the p.G188X-OTX2 protein had reduced ( approximately 50%) transactivation functions for the four promoters, with no dominant-negative effect. cDNA screening identified positive OTX2 expression in the hypothalamus. CONCLUSIONS: The results imply that OTX2 mutations are associated with variable pituitary phenotype, with no genotype-phenotype correlations, and that OTX2 can transactivate GNRH1 as well as HESX1 and POU1F1.

DOI： 10.1210/jc.2009-1334

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Noonan syndrome is characterized by facial dysmorphology, congenital heart disease and growth failure. Although it is also accompanied by deranged lymph-vessel formation, protein-losing enteropathy (PLE) with Noonan syndrome is rarely reported. We report clinical information about a boy with Noonan syndrome and late-onset lymphedema and PLE after standing for long periods of time during athletic practice sessions. The boy recovered from lymphedema and PLE after administration of 2.5 g of albumin followed by resting and raising his legs. They did not recur after he began walking again. Standing for long periods of time congested the lymph stream at the abdominal lymph vessel, whose formation is frequently disturbed in Noonan syndrome, and the increased pressure caused lymphedema and PLE. PLE is one of the clinical manifestations of Noonan syndrome.

DOI： 10.1297/cpe.18.87

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL PUBLISHING, INC  

BACKGROUND: Osteogenesis imperfecta (OI) is a heritable bone disease characterized by bone brittleness and various degrees of growth disorder. Cyclic pamidronate therapy is reportedly useful to prevent bone fracture in OI and in infants with OI, but, it remains unclear how infants with OI grow during bisphosphonate therapy. METHODS: Height and weight measurements of OI infants treated with cyclic pamidronate therapy were taken before and every 6 months during therapy until 18 months. Vertebral morphometry and the concavity index were analyzed using X-ray films taken simultaneously. RESULTS: Among OI patients, those in the group for which the height z-score decreased tended to have more femur fractures than those of the group for which the height z-score increased. Morphometry of the lumbar spine showed that compression fractures occurred less during cyclic pamidronate therapy, by which the lumbar bone mineral density increased. CONCLUSIONS: Bisphosphonate preserved vertebral morphometry during 18 months after starting therapy in infants. Prevention of femur fracture during the infantile period might help prevent short stature; therapeutic strategies during infancy must better emphasize prevention of long bone fracture before the beginning of gait.

DOI： 10.1111/j.1442-200X.2008.02649.x

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER JAPAN KK  

Patients with osteogenesis imperfecta (OI) show various degrees of bone fragility. Nevertheless, details of the mechanisms causing bone fragility remain unclear. We hypothesized that differences in pyridinoline cross-link formation at the N-and C-termini in type I collagen molecules partly contribute to bone fragility of OI. To verify this hypothesis, urinary N and C terminal telopeptides of type I collagen (uNTx and ubetaCTx, respectively) and urinary hydroxyproline (uHyp) were measured using second morning void urine samples obtained from OI patients and healthy control children. Ratios of uNTx and ubetaTx to uHyp (uNTx/uHyp and ubetaCTx/uHyp, respectively) of OI patients and healthy normal control children were analyzed. Ratios of uNTx to ubetaCTx (uNTx/ubetaCTx) were also analyzed. In OI patients, uNTx and ubetaCTx were lower than in healthy control children. Also, uNTx/uHyp and ubetaCTx/uHyp were significantly lower than in healthy children. Among OI patients, uNTx/uHyp and uNTx/ubetaCTx of type III OI were significantly lower than of either type I or type IV OI. These results show that pyridinoline cross-link formation is lower than in healthy control children and that pyridinoline cross-link formation at the N-and C-termini in type I collagen molecules might be differently disrupted in OI patients according to the severity of OI.

DOI： 10.1007/s00774-007-0827-z

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BLACKWELL PUBLISHING  

BACKGROUND: Osteogenesis imperfecta (OI) is an autosomal dominant disorder of connective tissue characterized by bone fragility and low bone mass. COL1A1 and COL1A2 genes are very large and have been rarely analyzed systematically in Japan. The aim of this project was to develop an effective and convenient method of finding mutations in the COL1A1 and COL1A2 gene by using denaturing high-performance liquid chromatography (DHPLC). METHODS: Polymerase chain reaction (PCR) amplicons of genomic DNA from the COL1A1 or COL1A2 gene were followed by heteroduplex analysis by DHPLC. Products containing heteroduplexes were then sequenced. RESULTS: Twenty-two OI families were analyzed, and 193 of the 1122 PCR products in the COL1A1 gene, all containing heteroduplexes, were sequenced. Sixty-two samples had single-base substitutions or single-base deletions or insertions within introns. Eight had single-base substitutions in exons. Six were pathogenic mutations, and two were silent mutations. In 16 families not identified with pathogenic mutation in COL1A1, COL1A2 was similarly analyzed. A total of 138 of the 848 PCR products were sequenced, and 46 samples had single-base substitutions, or single-base deletions or insertions within introns. Twenty-four samples had single-base substitutions in exons. Three were pathogenic mutations and the others silent. CONCLUSIONS: Mutations were identified in nine COL1A1/COL1A2 associated with OI type I-IV genes by scanning with DHPLC. Software was used to detect point mutation and large deletions/insertions in COL1A1 and COL1A2 genes.

DOI： 10.1111/j.1442-200X.2007.02422.x

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Total pages：357   Language：Japanese

CiNii Books

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Total pages：25p  

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Language：Japanese   Publisher：日本小児高血圧研究会  

【背景】一過性の著明な血圧上昇をきたし種々の身体症状を呈する症例において,褐色細胞腫の可能性は考慮する必要があるが,偽性褐色細胞腫との鑑別を要することもある.他方,その他の疾患と悩まれることは多くないが,今回我々は本態性高血圧に加えて精神的要因が関与したことにより褐色細胞腫に類似した症状を呈した症例を経験したため報告する.【症例】生来健康な男児で肥満はなかった.15歳時に学校で誘因なく発作的に胸部違和感を自覚した後上肢の脱力をきたし,更に意識混濁した.その際に保健室で測定された収縮期血圧は200mmHgを超えていた.同様のエピソードを反復したため当院に紹介された.来院時の血圧は140-150/70-80mmHg程度であった.問診では,学校生活での強い心理的ストレスの他,塩分摂取過多が疑われた.鑑別疾患として褐色細胞腫や偽性褐色細胞腫も考えられたが,意識混濁の身体症状を伴ったためてんかんの可能性も検討した.メタネフリンやカテコラミンの測定値や画像検査で異常はなく,上記エピソードが起こった際の心電図や脳波所見にも異常はなかった.他方,brachial-ankle Pulse Wave Velocityは両側とも高値であった.また,意識混濁を含む身体症状は精神科より解離性障害が疑われた.これらのことから,本態性高血圧が背景にあり,精神的要因が加わって一過性に高血圧になった可能性を考えた.食事指導とアムロジピンを少量から開始し増量した他,精神科からはクロチアゼパムが処方された.その後しばらくは,上記と同様のエピソードを繰り返し何度か当院に救急搬送されたが,次第に症状は落ち着いた.【考察】本症例は,褐色細胞腫に類似した症状を呈したが,身体症状として意識混濁を伴った点も特徴的であった.意識混濁は褐色細胞腫や偽性褐色細胞腫の身体症状としては考えにくく,てんかん性疾患も考えたが否定的であった.精神的要因で身体症状を伴って一過性に高血圧を呈することはあるが,その際の血圧上昇の程度は軽度とされている.このため,精神症状のみでは本症例の症状を説明できなかったが,本態性高血圧が背景にあり,解離様の精神症状が加わったことで褐色細胞腫類似の症状を呈したものと考えることで症状が説明づけられた.(著者抄録)

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DOI： 10.1038/s41598-022-11823-3

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Authorship：Lead author   Language：Japanese   Publisher：(株)東京医学社  

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Language：Japanese   Publisher：(一社)日本集中治療医学会  

6歳男児。1年前に頭蓋咽頭腫に対して開頭腫瘍摘出術を施行された。今回、頭蓋咽頭腫の再発に対して再度摘出術を施行され、術後2日目に意識障害が出現し、血清Na値が182mmol/Lまで上昇した。中枢性尿崩症と考え、生理食塩水とバソプレシンの持続静注を開始した。術後3日目以降は意識レベルが回復していたが、7日目に意識障害が再度出現し、血清Na値が142mmol/Lまで低下していたため、浸透圧性脱髄症候群を鑑別に挙げて頭部MRIを施行し、橋外性髄鞘崩壊症と診断した。本例は頭蓋咽頭腫が視床下部に強く癒着しており、腫瘍摘出に伴い視床下部機能障害が生じたことで高Na血症が急速に進行したものと考えられた。

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J02874&link_issn=&doc_id=20210611380012&doc_link_id=10.3918%2Fjsicm.28_227&url=https%3A%2F%2Fdoi.org%2F10.3918%2Fjsicm.28_227&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

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J-GLOBAL

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Authorship：Lead author   Language：Japanese   Publisher：(株)診断と治療社  

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J-GLOBAL

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J-GLOBAL

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Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)   Publisher：(株)東京医学社  

＜Key Points＞(1)Ellsworth-Howard試験はPTH濃度や臨床徴候、家族歴などからの偽性副甲状腺機能低下症と副甲状腺機能低下症の鑑別が困難な場合に行う。(2)PTH投与後のcAMPの増加反応には信頼性があり診断に有用である。(3)尿中リン酸排泄は健常人でも35mg/m2/2時間を下回る者も多く、その解釈には注意が必要である。(著者抄録)

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Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)   Publisher：(株)東京医学社  

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Language：Japanese   Publisher：(一社)日本骨代謝学会  

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Language：Japanese   Publisher：(株)医学書院  

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Language：Japanese   Publisher：(公社)日本小児科学会  

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Language：Japanese   Publisher：(一社)日本骨代謝学会  

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Language：Japanese   Publisher：(公社)日本小児科学会  

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Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)   Publisher：(株)総合医学社  

＜point＞易骨折性をきたす小児疾患は多岐にわたり、先天性疾患では骨形成不全症の頻度が最も高い。骨形成不全症の診断は病歴、身体所見、家族歴、X線所見などを総合して行うことが重要である。海外の報告では、小児の骨折のうち虐待による骨折は1歳半未満に多く、非虐待骨折は5歳以上に多い。虐待に伴った骨折に100%の特異性をもつ骨折の種類や部位はなく、病歴や身体所見などを基に器質的な疾患を除外し、多職種で慎重に診断、対応することが重要である。(著者抄録)

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Language：Japanese   Publisher：岡山大学大学院教育学研究科・心理教育相談室  

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Language：Japanese   Publisher：(有)医学の世界社  

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Language：Japanese   Publisher：(株)診断と治療社  

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2011&ichushi_jid=J00642&link_issn=&doc_id=20110426240054&doc_link_id=%2Fae4shond%2F2011%2F0074s1%2F054%2F0363-0369%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fae4shond%2F2011%2F0074s1%2F054%2F0363-0369%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

J-GLOBAL

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Language：Japanese   Publisher：(株)医薬ジャーナル社  

骨形成不全症(osteogenesis imperfecta:以下、OIと略す)はさまざまな程度の骨の脆弱性をきたし、象牙質形成不全、青色強膜、成長障害、聴力障害などの臨床症状を伴う疾患である。大部分のOIはCOL1A1遺伝子およびCOL1A2遺伝子によりひきおこされるが、CRTAP、LEPRE1、PPIB、SERPINH1、FKBP10などI型コラーゲン分子の修飾に関わる遺伝子が原因となるOIも同定されている。一方でV型、VI型のように原因遺伝子の判明していないOIも存在する。OIの疾患分類には古くからSillenceらによる分類が用いられていたが、新しい原因遺伝子の発見により疾患分類にもさまざまな提案がなされている。(著者抄録)

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Language：Japanese   Publisher：(株)日本小児医事出版社  

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2010&ichushi_jid=J00643&link_issn=&doc_id=20100607160005&doc_link_id=%2Fag1snrsd%2F2010%2F006306%2F006%2F1097-1104%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fag1snrsd%2F2010%2F006306%2F006%2F1097-1104%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

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Language：Japanese   Publisher：(有)医学の世界社  

OTX2遺伝子異常症の詳細な臨床スペクトラムを明らかにする目的で、無・小眼球症、視神経低形成患者28名(下垂体機能低下症合併例16名を含む)、眼症状のない下垂体機能低下症患者66名を対象に、OTX2変異・欠失解析、機能解析、変異・欠失陽性患者の臨床像、OTX2の発現解析を行った。その結果、3種の新規OTX2フレームシフト変異、1種の新規ナンセンス変異、OTX2を含む微小欠失をヘテロ接合性に同定した。OTX2ヘテロ異常症は全例で無・小眼球症と発達遅滞を認め、正常からGHD、CPHDまでの多様な下垂体表現型を示した。POU1F1、GNRH1のヘテロ結合性異常では、表現型は正常であった。OTX2はヒトにおいてもGNRH1プロモーターの転写活性化作用があり、性腺機能に関与する可能性を示唆した。以上より、OTX2は下垂体機能低下症の原因遺伝子であり、正常からGHD、CPHDまで多様な下垂体表現型を示すことがわかった。

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Language：Japanese   Publisher：(公社)日本小児科学会  

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CiNii Article

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Other Link： http://search.jamas.or.jp/link/ui/2008098867

Language：Japanese   Publisher：(有)科学評論社  

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Language：Japanese   Publisher：(有)医学の世界社  

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Language：Japanese   Publisher：診断と治療社  

CiNii Article

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Other Link： http://search.jamas.or.jp/link/ui/2003306544

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CiNii Article

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Other Link： http://search.jamas.or.jp/link/ui/2003141275

Language：Japanese   Publisher：松山赤十字病院医学雑誌編集部  

症例1は12歳男児で,咳が続き,その後発熱,嘔吐,頭痛が出現し入院となった.症例2は13歳男.咳嗽,発熱ののち蕁麻疹が出現し,その後嘔吐,頭痛が出現したため入院となった.2例とも入院時,項部硬直とケルニッヒ徴候を認めた.又,両例ともマイコプラズマ抗体価が10240倍と著明に増加しており,髄液培養は陰性であった.症例1はミノサイクリン静注とクラリスロマイシン内服を,症例2はミノサイクリン内服を行い症状の改善をみた

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Event date： 2022.5.14

Language：Japanese   Presentation type：Oral presentation (general)  

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Event date： 2022.4

Language：Japanese  

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Event date： 2022.4

Language：Japanese  

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Event date： 2022.4

Language：Japanese  

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Event date： 2022.4

Language：Japanese  

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Event date： 2022.1.21

Language：Japanese   Presentation type：Oral presentation (invited, special)  

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Event date： 2021.12.3 - 2021.12.4

Language：Japanese   Presentation type：Public lecture, seminar, tutorial, course, or other speech  

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Event date： 2021.11.26 - 2021.11.27

Language：Japanese   Presentation type：Oral presentation (invited, special)  

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Event date： 2021.10.28 - 2021.10.30

Language：Japanese  

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Event date： 2021.10.15

Language：Japanese   Presentation type：Oral presentation (invited, special)  

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Event date： 2021.9.11

Language：Japanese   Presentation type：Oral presentation (invited, special)  

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Event date： 2021.8.22

Language：Japanese   Presentation type：Oral presentation (general)  

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Event date： 2021.6.23

Language：Japanese   Presentation type：Oral presentation (invited, special)  

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Event date： 2021.6.11

Language：Japanese   Presentation type：Oral presentation (invited, special)  

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Event date： 2021.6

Language：Japanese  

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Event date： 2021.5

Language：Japanese  

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Event date： 2021

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Event date： 2021

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Event date： 2021

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Event date： 2021

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Event date： 2021

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Event date： 2021

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Event date： 2020.12.1

Language：Japanese   Presentation type：Oral presentation (invited, special)  

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Event date： 2020.11.28

Language：Japanese   Presentation type：Poster presentation  

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Event date： 2020.10.4

Language：Japanese  

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Event date： 2020.10.1 - 2020.10.31

Language：Japanese   Presentation type：Oral presentation (invited, special)  

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Event date： 2020.8.31

Language：Japanese   Presentation type：Poster presentation  

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Event date： 2020.8

Language：Japanese  

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Event date： 2020.7.20 - 2020.8.31

Language：Japanese   Presentation type：Poster presentation  

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Event date： 2020.7.20 - 2020.8.31

Language：Japanese   Presentation type：Poster presentation  

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Event date： 2020.7.20 - 2020.8.31

Presentation type：Poster presentation  

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Event date： 2020.1

Language：Japanese  

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Event date： 2020

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Event date： 2020

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Event date： 2020

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Event date： 2020

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Event date： 2019.11.29 - 2019.11.30

Language：Japanese   Presentation type：Oral presentation (general)  

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Event date： 2019.10

Language：Japanese  

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Event date： 2019.9.28

Language：Japanese   Presentation type：Poster presentation  

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Event date： 2019.9.26 - 2019.9.28

Language：Japanese  

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Event date： 2019.9.26 - 2019.9.28

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

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Event date： 2019.9.26 - 2019.9.28

Language：Japanese   Presentation type：Poster presentation  

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Event date： 2019.9.26 - 2019.9.28

Language：Japanese   Presentation type：Public lecture, seminar, tutorial, course, or other speech  

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Event date： 2019.9.7

Language：Japanese  

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Event date： 2019.9.7

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Event date： 2019.8.24

Language：Japanese   Presentation type：Oral presentation (invited, special)  

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Event date： 2019.7.18

Language：Japanese   Presentation type：Oral presentation (invited, special)  

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Event date： 2019.6.8

Language：Japanese   Presentation type：Oral presentation (general)  

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Event date： 2019.5.9 - 2019.5.11

Language：Japanese   Presentation type：Oral presentation (general)  

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Event date： 2019

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Event date： 2019

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Event date： 2018.6.14 - 2018.6.16

Presentation type：Public lecture, seminar, tutorial, course, or other speech  

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Event date： 2018.6

Language：Japanese  

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Event date： 2018.4.26 - 2018.4.28

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Event date： 2017.12.3

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Event date： 2017.12.2

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Event date： 2017.9.28 - 2017.9.30

Presentation type：Poster presentation  

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Event date： 2017.9.28 - 2017.9.30

Presentation type：Symposium, workshop panel (nominated)  

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Event date： 2017

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Event date： 2015.10

Language：English  

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Event date： 2015.8.21 - 2015.8.22

Presentation type：Poster presentation  

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Event date： 2015.4.15 - 2015.4.18

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Event date： 2015

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Event date： 2014.7.26

Presentation type：Poster presentation  

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Event date： 2014.4.24 - 2014.4.26

Presentation type：Oral presentation (general)  

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Event date： 2011.11.19

Presentation type：Oral presentation (general)  

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Event date： 2011.11.5 - 2011.11.6

Presentation type：Oral presentation (general)  

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Event date： 2011.11.3 - 2011.11.5

Presentation type：Symposium, workshop panel (nominated)  

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Event date： 2011.8.12 - 2011.8.14

Presentation type：Oral presentation (general)  

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Event date： 2011.2.10

Presentation type：Oral presentation (general)  

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Event date： 2010.10.2

Presentation type：Oral presentation (general)  

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Event date： 2010.6.19 - 2010.6.22

Language：English   Presentation type：Poster presentation  

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Event date： 2010.4.23 - 2010.4.25

Presentation type：Poster presentation  

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Event date： 2010.3.31 - 2010.4.1

Language：English   Presentation type：Oral presentation (general)  

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Event date： 2010.3.25 - 2010.3.28

Presentation type：Poster presentation  

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Event date： 2010.2.4

Presentation type：Oral presentation (general)  

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Event date： 2009.10.1 - 2009.10.3

Presentation type：Poster presentation  

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Event date： 2009.9.23 - 2009.9.26

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Event date： 2009.7.23 - 2009.7.25

Presentation type：Oral presentation (general)  

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Event date： 2009

Language：English  

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Event date： 2007.11.7 - 2007.11.9

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Event date： 2007.10.20

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Event date： 2005.11.5

Language：Japanese  

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Event date： 2005

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Event date： 2003.12.30

Language：Japanese  

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Event date： 2002.9

Language：Japanese  

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Event date： 2002.4

Language：Japanese  

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Language：Japanese   Presentation type：Oral presentation (invited, special)  

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Language：Japanese   Presentation type：Oral presentation (general)  

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Language：Japanese   Presentation type：Oral presentation (invited, special)  

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Presentation type：Oral presentation (invited, special)  

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Presentation type：Oral presentation (general)  

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Presentation type：Oral presentation (general)  

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Language：Japanese   Presentation type：Oral presentation (general)  

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Language：Japanese   Presentation type：Oral presentation (general)  

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Presentation type：Oral presentation (general)  

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Presentation type：Oral presentation (general)  

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Language：Japanese   Presentation type：Oral presentation (general)  

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Language：Japanese   Presentation type：Oral presentation (invited, special)  

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Language：Japanese   Presentation type：Oral presentation (general)  

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Presentation type：Oral presentation (general)  

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Language：Japanese   Presentation type：Oral presentation (general)  

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