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Biomedical subjects

Tomonobu Hasegawa

Publications and source records attributed to Tomonobu Hasegawa.

At least 19 recordsLinked to original sources
PubMed2006

Age-dependent percentile for waist circumference for Japanese children based on the 1992-1994 cross-sectional national survey data.

The aim of this study was to set forth an age-dependent percentile for waist circumference of Japanese children and to compare the reference with data from other countries. We utilized the 1992-1994 cross-sectional national survey data on waist circumference as measured at two benchmark sites in 10,614 Japanese children (5,851 boys, 4,763 girls) aged 6.0-18.0 years for constructing the reference by the LMS method. Japanese children had smaller waist circumference percentile values as compared to those of Dutch and US children, but had comparable or larger percentile values as compared to those of UK children. We suspect that the observed ethnic differences may be in part due to the differences in benchmark in waist circumference measurements in each country. We present for the first time an age-dependent percentile for waist circumference for Japanese children. It is mandatory to standardize a benchmark site for waist circumference for more meaningful international comparison.

Adolescent↗
PubMed2006

CXorf6 is a causative gene for hypospadias.

46,XY disorders of sex development (DSD) refer to a wide range of abnormal genitalia, including hypospadias, which affects approximately 0.5% of male newborns. We identified three different nonsense mutations of CXorf6 in individuals with hypospadias and found that its mouse homolog was specifically expressed in fetal Sertoli and Leydig cells around the critical period for sex development. These data imply that CXorf6 is a causative gene for hypospadias.

Animals↗
PubMed2006

Urine steroid hormone profile analysis in cytochrome P450 oxidoreductase deficiency: implication for the backdoor pathway to dihydrotestosterone.

CONTEXT: Although the "backdoor" pathway to dihydrotestosterone has been postulated in the fetal-to-early-infantile period of patients with cytochrome P450 oxidoreductase deficiency (PORD), clinical data in support of this pathway remain limited. OBJECTIVE: The objective of this study was to obtain clinical evidence for the presence of the backdoor pathway in PORD. SETTING: This was a collaboration study between laboratories and hospitals. SUBJECTS: Twenty-two Japanese patients with molecularly confirmed PORD and 1763 control subjects participated in this study. INTERVENTION: Urine steroid profile analysis was performed by gas chromatography/mass spectrometry. In five patients and 776 control subjects, urine samples were obtained before 12 months of age. MAIN OUTCOME MEASURE: The main outcome measure was identification of a urine steroid(s) indicating the backdoor pathway. RESULTS: In the PORD patients, pregnanediol, pregnanetriolone, and pregnanetriol were obviously elevated, and the urine steroid ratios reflecting CYP17A1 and CYP21A2 activities were decreased throughout the examined ages. Furthermore, etiocholanolone and 11-hydroxyandrosterone, which should originate almost exclusively from androstenedione in the conventional "frontdoor" pathway, were grossly normal or somewhat decreased since early infancy, whereas androsterone, which can be derived not only from androstenedione and dihydrotestosterone in the conventional frontdoor pathway but also from 5alpha-pregnane-3alpha,17alpha-diol-20-one in the backdoor pathway, was increased during early infancy and remained grossly normal thereafter. Thus, the androsterone to etiocholanolone ratio was increased during early infancy and remained grossly normal thereafter. 5alpha-Pregnane-3alpha,17alpha-diol-20-one was elevated throughout the examined ages. CONCLUSIONS: The increased androsterone excretion during early infancy, as compared with the etiocholanolone and 11-hydroxyandrosterone excretions in the same period, suggests the presence of the backdoor pathway in PORD.

Adolescent↗
PubMed2006

Phenotypic spectrum of CHARGE syndrome with CHD7 mutations.

CHD7 gene mutations were identified in 17 (71%) of 24 children clinically diagnosed to have CHARGE syndrome (C, coloboma of the iris or retina; H, heart defects; A, atresia of the choanae; R, retardation of growth and/or development; G, genital anomalies; and E, ear abnormalities). Colobomata, hearing loss, laryngomalacia, and vestibulo-cochlear defect were prevalent. Molecular testing for CHD7 enables an accurate diagnosis and provides health anticipatory guidance and genetic counseling to families with CHARGE syndrome.

Abnormalities, Multiple↗
PubMed2006

Congenital hypothyroidism in Peters plus syndrome.

Peters plus syndrome is a multiple malformation syndrome characterized by a combination of Peters anomaly of the eye and other extraocular defects, including short-limb dwarfism, a thin upper lip, hypoplastic columella, and a round face. Two unrelated children with the typical features of Peters plus syndrome and hypothyroidism have been previously reported in medical literature. Herein, we report a male patient who exhibited the Peters plus syndrome phenotype as well as hypothyroidism and provide further evidence that hypothyroidism may represent an under-recognized feature of Peters plus syndrome. The consanguinity of the parents in the present case supports, but does not confirm, the notion that a homozygous defect in a single autosomal recessive gene might be responsible for the normal morphogenesis of both the anterior chamber and the thyroid gland.

Abnormalities, Multiple↗
PubMed2006

Growth-chart-based qualitative evaluation of height growth after hematopoietic stem cell transplantation.

Growth failure is one of the most common late complications in children undergoing hematopoietic stem cell transplantation (SCT). The present report describes a qualitative method of evaluating height growth after SCT, using a growth chart. The patients were divided into three groups according to the shape of their growth chart: the normal growth chart group, the early-onset growth retardation group (E-group), in which a decreased growth rate was seen during the first year after SCT, and the late-onset growth retardation group (L-group), in which a decreased growth rate was seen more than 1 yr after the SCT. In the E-group, total body irradiation and prolonged steroid therapy were thought to contribute to the growth failure, whereas in the L-group, impaired pubertal development was thought to be responsible. The growth pattern in the L-group may, therefore, be of particular clinical importance, because the final stature of the subjects in this group can be improved by pharmacological adjustment of pubertal onset. Although limited by the small size and heterogeneous nature of the sample, our results suggest that growth-chart-based evaluation may provide important information to stratify subjects showing inadequate growth after SCT into two groups whose follow-up and treatment should be individualized.

Adolescent↗
PubMed2006

Cytochrome P450 oxidoreductase deficiency in three patients initially regarded as having 21-hydroxylase deficiency and/or aromatase deficiency: diagnostic value of urine steroid hormone analysis.

In this study, we report on three Japanese patients with cytochrome P450 oxidoreductase (POR) deficiency (PORD). Case one was a 46,XY patient who was found to have mildly increased 17alpha-hydroxyprogesterone (17-OHP) by the neonatal mass screening. There was no maternal virilization during pregnancy, and he had no skeletal or genital abnormality. Thus, he was initially diagnosed as having nonclassical 21-hydroxylase deficiency (21-OHD). Cases two and three were 46,XX patients who were identified because of severely virilized external genitalia and maternal virilization during pregnancy. In case two, the neonatal mass screening was normal, and she had no skeletal abnormality except for mild adduction of bilateral third toes. Thus, she was initially diagnosed as having aromatase deficiency. In case three, the neonatal mass screening showed moderately increased 17-OHP, and no skeletal lesion other than rigid second metacarpophalangeal joints was identified in early infancy. Thus, she was initially suspected as having 21-OHD and/or aromatase deficiency. Subsequently, endocrine studies including urine steroid hormone analysis were performed for the assessment of glucocorticoid treatment in case one and for the virilized genitalia in cases two and three, showing adrenal and/or gonadal dysfunction characteristic of PORD. Thus, molecular analysis of POR was carried out, demonstrating homozygosity for R457H in cases one through three. The results imply that clinical features in PORD can be similar to those in 21-OHD or aromatase deficiency, and that comprehensive assessment of the pregnant course, physical examination, and adrenal and gonadal function studies is essential for the precise diagnosis of PORD.

17-alpha-Hydroxyprogesterone↗
PubMed2005

Analysis of the NSD1 promoter region in patients with a Sotos syndrome phenotype.

Sotos syndrome (SoS, OMIM#117550) is an overgrowth disorder characterized by excessive growth-especially in the first years of childhood-distinctive craniofacial features, and various degrees of mental retardation. Haploinsufficiency of the nuclear receptor binding SET domain containing protein 1 (NSD1) gene, due to either intragenic mutations or whole-gene microdeletions, is found in the majority of patients with SoS. However, in approximately 10-40% of patients with a typical SoS phenotype, no abnormalities are detected. In this study, hemizygous hypermethylation or genomic sequence abnormalities of the promoter region of NSD1 were hypothesized to be the underlying cause in patients with a SoS phenotype, but without confirmed NSD1 alterations. In 18 patients, including one patient with a reported hepatocellular carcinoma, the promoter region of NSD1 was analyzed. However, no hypermethylation or sequence abnormalities in the promoter region could be detected. It therefore seems unlikely that such abnormalities of NSD1 are a major culprit in patients with phenotypical SoS. Additional methods are necessary for detection of other genetic or epigenetic causes of SoS.

Base Sequence↗
PubMed2005

Association of cryptorchidism with a specific haplotype of the estrogen receptor alpha gene: implication for the susceptibility to estrogenic environmental endocrine disruptors.

CONTEXT: The prevalence of cryptorchidism (CO) has increased during the past few decades in several countries, and this event has primarily been ascribed to the estrogenic effects of environmental endocrine disruptors (EEDs). Little is known, however, about the role of genetic susceptibility to EEDs in this phenomenon. OBJECTIVE: The objective of this study was to determine whether CO is associated with a specific haplotype of the gene for estrogen receptor alpha (ESR1) that mediates the estrogenic effects of EEDs. DESIGN: This was a case-control study. SETTING: The study was performed at the National Research Institute and University Hospitals. SUBJECTS: Sixty-three cryptorchid males, aged 1-13 yr, and 47 control males, aged 4-12 yr, were studied. INTERVENTION: After genotyping 15 single nucleotide polymorphisms widely distributed in the greater than 300-kb genomic sequences of ESR1, haplotype analysis was performed. MAIN OUTCOME MEASURE: Identification of a specific ESR1 haplotype associated with CO was the main outcome measure. RESULTS: A haplotype block was identified for an approximately 50-kb region encompassing single nucleotide polymorphisms 10-14 in the 3' region of ESR1 in both groups. The frequency of the estimated AGATA haplotype within the block was higher in the patients than in the control males (34.0% vs. 21.3%; P = 0.037), and the association of this haplotype with CO phenotype was significant in a recessive mode (P = 0.0060). The homozygosity for this haplotype was identified only in the patients, and the frequency of the homozygotes was significantly different between the two groups (10 of 63 vs. zero of 47; P = 0.0042). CONCLUSIONS: The association of CO with homozygosity for the specific ESR1 haplotype suggests the relevance of genetic susceptibility to EEDs in the development of CO.

Adolescent↗
PubMed2005

Gonadotrophin therapy in Kallmann syndrome caused by heterozygous mutations of the gene for fibroblast growth factor receptor 1: report of three families: case report.

Gonadotrophin therapy (GT) is frequently used to induce fertility in Kallmann syndrome (KS). We studied the effects and the consequences of GT in autosomal dominant KS caused by heterozygous FGFR1 mutations. Three Japanese families were examined. In family A, an adult male received GT and had two sons. In family B, an adult female received GT and gave birth to dizygotic male and female twins. In family C, an adult female received GT and produced a son and a daughter. Direct sequencing was performed for FGFR1, and clinical assessment was carried out for KS features. The father and the elder son of family A had P745S mutation, the mother and the female twin of family B had G687R mutation, and the mother and the two children of family C had S107X mutation. KS phenotype was detected for the mutation-positive subjects, except for the elder son of family A who had apparently normal phenotype. GT in FGFR1 mutations is effective in acquiring fertility but has a risk of transmitting the mutation and the disease phenotype to the next generation.

Adult↗
PubMed2005

Association of severe micropenis with Gly146Ala polymorphism in the gene for steroidogenic factor-1.

Steroidogenic factor-1 (SF-1) regulates the transcription of multiple genes involved in the androgen biosynthesis, and SF-1 Gly146Ala polymorphism is known to reduce the transactivation function by approximately 20%. To examine whether the Gly146Ala polymorphism constitutes a susceptibility factor for the development of micropenis (MP), we analyzed this polymorphism in a total of 52 patients with micropenis (T-MP) consisting of 30 patients with severe MP below -2.5 SD (S-MP) and 22 patients with mild MP from -2.1 SD to -2.5 SD (M-MP), together with 115 control males. The Ala allele, the Ala/Gly genotype, and the Ala/Ala plus Ala/Gly genotype frequencies were significantly higher in the S-MP patients than in the control males, whereas the allele and the genotype frequencies were comparable between the M-MP patients and the control males. The results suggest that the SF-1 Gly146Ala polymorphism may constitute a susceptibility factor for the development of S-MP, and that M-MP can be regarded as a normal variation in terms of the polymorphism effect.

Adolescent↗
PubMed2005

Association of micropenis with Pro185Ala polymorphism of the gene for aryl hydrocarbon receptor repressor involved in dioxin signaling.

The prevalence of undermasculinized external genitalia has increased in several countries including Japan, and this phenomenon has primarily been ascribed to the deleterious effects of environmental endocrine disruptors such as dioxins. To examine a possible role of the genetic susceptibility to dioxins in the development of micropenis (MP), we studied the Arg554Lys polymorphism of the gene for aryl hydrocarbon receptor (AHR) and the Pro185Ala polymorphism of the gene for aryl hydrocarbon receptor repressor (AHRR), in 73 boys with MP (34 boys with mild MP from -2.1 to -2.5 SD and 39 boys with severe MP below -2.5 SD) and 80 control males (50 boys and 30 fertile adult males). The allele and genotype frequencies of the AHR polymorphism were comparable between the two groups of males, but those of the AHRR polymorphism were significantly different, with the Pro allele and the Pro/Pro genotype being more frequent in boys with MP than in control males (P-value: 0.0029 for the allele frequency and 0.011 for the genotype frequency). In addition, both polymorphisms were comparable in the allele and genotype frequencies between boys with mild MP and those with severe MP and between control boys and control fertile adult males. The results suggest that the AHRR Pro185Ala polymorphism may constitute a susceptibility locus for the development of MP in response to dioxins.

Adolescent↗