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Tsutomu Ogata

Publications and source records attributed to Tsutomu Ogata.

At least 19 recordsLinked to original sources
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

Mutation and polymorphism analyses of INSL3 and LGR8/GREAT in 62 Japanese patients with cryptorchidism.

BACKGROUND/AIMS: Although insulin-like factor 3 (INSL3) and its receptor leucine-rich repeat-containing G protein-coupled receptor 8/G protein-coupled receptor affecting testis descent (LGR8/GREAT) are essential for the gubernacular development, mutations of INSL3 and LGR8/GREAT are infrequent in patients with cryptorchidism (CO), and there is no report documenting a positive association of CO with a polymorphism in INSL3 or LGR8/GREAT. Here, we further examined the relevance of INSL3 and LGR8/GREAT mutations and polymorphisms to the development of CO. METHODS: Sixty-two Japanese CO patients and 60 fertile males were studied. INSL3 was analyzed by direct sequencing and restriction enzyme digestion, and LGR8/GREAT was examined by denaturing high-performance liquid chromatography followed by direct sequencing for exons with abnormal chromatogram patterns. RESULTS: No definitive mutation was identified in both genes. Six polymorphisms were detected in INSL3 or LGR8/GREAT and Thr/Thr genotype of Ala60Thr polymorphism in INSL3 was strongly associated with CO (p=0.0024, odds ratio=5.3, 95% confidence interval=1.7-17). CONCLUSION: The results, in conjunction with the previous data, suggest that mutations of INSL3 and LGR8/GREAT remain rare, and that the Thr/Thr genotype of Ala60Thr polymorphism in INSL3 may constitute a susceptibility factor for the development of CO.

Adolescent↗
PubMed2006

Kallmann syndrome phenotype in a female patient with CHARGE syndrome and CHD7 mutation.

We report on a 14 7/12-year-old Japanese female patient with CHARGE syndrome and CHD7 mutation who also exhibited Kallmann syndrome (KS) phenotype. She had poor pubertal development and apparently impaired sense of smell. A GnRH test showed severely compromised responses of LH (<0.5 --> <0.5 IU/L) and FSH (<0.5 --> 1.2 IU/L), and magnetic resonance imaging delineated hypoplastic olfactory bulbs. Mutation analysis revealed a heterozygous nonsense mutation at exon 33 of CHD7 (7027C>T, Q2343X). The results provide further support for the notion that KS phenotype can be included in the phenotypic spectrum of CHARGE syndrome, and indicate that CHARGE syndrome with KS phenotype is caused by a CHD7 mutation.

Abnormalities, Multiple↗
PubMed2006

Comprehensive genetic analysis of relevant four genes in 49 patients with Marfan syndrome or Marfan-related phenotypes.

In order to evaluate the contribution of FBN1, FBN2, TGFBR1, and TGFBR2 mutations to the Marfan syndrome (MFS) phenotype, the four genes were analyzed by direct sequencing in 49 patients with MFS or suspected MFS as a cohort study. A total of 27 FBN1 mutations (22 novel) in 27 patients (55%, 27/49), 1 novel TGFBR1 mutation in 1 (2%, 1/49), and 2 recurrent TGFBR2 mutations in 2 (4%, 2/49) were identified. No FBN2 mutation was found. Three patients with either TGFBR1 or TGFBR2 abnormality did not fulfill the Ghent criteria, but expressed some overlapping features of MFS and Loeys-Dietz syndrome (LDS). In the remaining 19 patients, either of the genes did not show any abnormalities. This study indicated that FBN1 mutations were predominant in MFS but TGFBRs defects may account for approximately 5-10% of patients with the syndrome.

Activin Receptors, Type I↗
PubMed2006

Determination of specific activities and kinetic constants of biotinidase and lipoamidase in LEW rat and Lactobacillus casei (Shirota).

Enzyme kinetic parameters, such as K(m), V(max) (or V), k(cat)/K(m), and K(i) (by biotin or lipoic acid) for biotinidase and lipoamidase were determined in Lewis (LEW) rat and Lactobacillus casei (Shirota) using fluorimetric high-performance liquid chromatography (HPLC). It was found that the final protein concentration below 0.1mg/ml is sufficient to obtain linear hydrolytic reaction and to determine the Michaelis-Menten type kinetic parameters (K(m), V, K(i)). We applied this HPLC enzyme assay method onto the rat and some bacteria. The highest specific activities (Vs) for biotinidase were found in Lactobacillus casei (Shirota) and rat kidney. It was also found that the largest K(i) by product for biotinidase and lipoamidase were present in the Lactobacillus casei (Shirota). There has been found specie (between rat and mouse) differences and tissue (organ) differences, together with tissue region differences and sex differences in some tissues. Summary of the distributions of both enzymes in LEW rat was also presented. Therefore, this HPLC determination method for the enzyme kinetic parameters in tissues is expected to be an indispensable tool for the investigation of the various diseases in humans.

Amidohydrolases↗
PubMed2006

Identification of novel RMRP mutations and specific founder haplotypes in Japanese patients with cartilage-hair hypoplasia.

Cartilage-hair hypoplasia (CHH), or metaphyseal dysplasia, McKusick type, is an autosomal recessive disease with diverse clinical manifestations. CHH is caused by mutations in RMRP (ribonuclease mitochondrial RNA processing), the gene encoding the RNA component of the ribonucleoprotein complex RNase MRP. A common founder mutation, 70A>G has been reported in the Finnish and Amish populations. We screened 11 Japanese patients with CHH for RMRP mutations and identified mutations in five probands, including three novel mutations (16-bp dup at +1, 168G>A, and 217C>T). All patients were compound heterozygotes for an insertion or duplication in the promoter or 5'-transcribed regions and a point mutation in the transcribed region. Two recurrent mutations were unique to the Japanese population: a 17-bp duplication at +3 and 218A>G. Haplotype analysis revealed that the two mutations common in Japanese individuals were contained within distinct haplotypes. Through this analysis, we have identified a unique mutation spectrum and founder mutations in the Japanese population.

Adolescent↗
PubMed2006

[Kallmann syndrome].

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Chorionic Gonadotropin↗
PubMed2006

[Noonan syndrome].

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Human Growth Hormone↗
PubMed2006

[XX male].

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Androgen Antagonists↗
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

Kallmann syndrome: somatic and germline mutations of the fibroblast growth factor receptor 1 gene in a mother and the son.

CONTEXT: Although Kallmann syndrome (KS) caused by heterozygous loss of function mutations of the fibroblast growth factor receptor 1 gene (FGFR1) is occasionally associated with characteristic features, such as dental agenesis and cleft palate, FGFR1 mutations remain unidentified in several KS patients with such characteristic features. SUBJECTS AND METHODS: We examined a 14-yr-old Japanese boy with hypogonadotropic hypogonadism, olfactory dysfunction, and dental agenesis and his fertile mother with olfactory dysfunction and dental agenesis. Direct sequencing was performed for FGFR1 using leukocyte genomic DNA from the proband and leukocyte and nail genomic DNA from the mother. To examine a possible somatic mutation, a specific forward primer was designed to introduce a BstXI site into the normal allele only, and nested PCR amplification, followed by BstXI digestion, was carried out three times with different reverse primers. RESULTS: After standard PCR amplifications, a heterozygous 2-bp deletion at exon 10 (1317_1318delTG), which is predicted to cause a frameshift at the 439th codon for serine and resultant termination at the 461st codon (S439fsX461), was identified in the proband, but was not found in the mother. After selective amplification of the mutant allele, this deletion was detected in nail DNA, but not in leukocyte DNA, from the mother. CONCLUSION: The results suggest that the 2-bp deletion took place as a somatic mutation in the mother and was transmitted to the boy because of germline mosaicism. Such a somatic mutation occurs in some apparently FGFR1 mutation-negative KS patients with dental agenesis.

Adolescent↗
PubMed2006

Imaging of congenital lipoid adrenal hyperplasia.

This article describes the specific radiological findings of congenital lipoid adrenal hyperplasia (lipoid CAH) in a phenotypic female and karyotypic 46XY infant. Radiological examination showed enlarged bilateral adrenal glands with fatty accumulation and spared medulla. These findings are key to differentiating lipoid CAH from the diseases that cause adrenal insufficiency during early infancy, including other forms of congenital adrenal hyperplasia.

Adrenal Hyperplasia, Congenital↗
PubMed2006

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

Genotyping analysis was performed for Gly146Ala polymorphism in the gene for steroidogenic factor-1 (SF-1), which is known to reduce the transactivation function by approximately 20%, in 72 cryptorchid patients and 136 control males, revealing that the Ala allele, the Ala/Gly genotype, and the Ala/Ala plus Ala/Gly genotype frequencies were significantly higher in the patients than in the control males. The results suggest that the Gly146Ala polymorphism may be a susceptibility factor for the development of cryptorchidism (CO).

Adolescent↗