Micropenis and the 5α-Reductase-2 (SRD5A2) Gene: Mutation and V89L Polymorphism Analysis in 81 Japanese Patients

abstract Uncoupling protein 2 (UCP2), a member of the family of mitochondrial carrier proteins, has been implicated in the control of whole-body energy balance. The coding region of the human UCP2 gene has now been shown to comprise six exons, and the sequences of the exon-intron boundaries were determined. With the use of this sequence information, 25 Japanese patients with obesity and noninsulin-dependent diabetes mellitus (NIDDM) and 25 subjects with simple obesity were screened for mutations in the entire coding region of UCP2 by PCR and single-strand conformation polymorphism analysis. Two nucleotide polymorphisms resulting in Ala55 → Val and Ala232 → Thr substitutions were detected. With the use of PCR and restriction fragment length polymorphism analysis, the allele frequencies for each of these polymorphisms were determined in 210 Japanese patients with NIDDM, 42 obese individuals, and 218 normal control subjects. The frequency of the Val55 allele did not differ significantly among the NIDDM group (46.0%), the obesity group (48.8%), and the normal control group (48.4%). The Thr232 allele was detected in only three subjects, who were heterozygotes and in the NIDDM group (allele frequency, 0.7%). However, expression in yeast of the human wild-type UCP2 protein and UCP2 containing Thr232 revealed no difference in functional activity. These results indicate that the Ala55 → Val and Ala232 → Thr variants of UCP2 do not play an important role in the pathogenesis of NIDDM or obesity in the Japanese population.

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Analysis of the PTEN gene mutation in polyposis syndromes and sporadic gastrointestinal tumors in Japanese patients

Diseases of the Colon & Rectum ◽

10.1007/bf02237223 ◽

2000 ◽

Vol 43 (Sup 10) ◽

pp. S29-S33 ◽

Cited By ~ 15

Author(s):

Kenichi Negoro ◽

Seiichi Takahashi ◽

Yoshitaka Kinouchi ◽

Sho Takagi ◽

Nobuo Hiwatashi ◽

...

Keyword(s):

Gene Mutation ◽

Japanese Patients ◽

Gastrointestinal Tumors ◽

Pten Gene ◽

Polyposis Syndromes

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Compound heterozygous CNGA3 mutations (R436W, L633P) in a Japanese patient with congenital achromatopsia

Visual Neuroscience ◽

10.1017/s095252380623308x ◽

2006 ◽

Vol 23 (3-4) ◽

pp. 395-402 ◽

Cited By ~ 22

Author(s):

SATOSHI GOTO-OMOTO ◽

TAKAAKI HAYASHI ◽

TAMAKI GEKKA ◽

AKIKO KUBO ◽

TOMOKAZU TAKEUCHI ◽

...

Keyword(s):

Visual Acuity ◽

Direct Sequencing ◽

Mutation Screening ◽

Venous Blood ◽

Japanese Patients ◽

White Background ◽

Compound Heterozygous ◽

Polymorphism Analysis ◽

Missense Mutations ◽

Α Subunit

Congenital achromatopsia is a stationary retinal disorder with autosomal recessive inheritance that is characterized by loss of color discrimination, low visual acuity, photophobia, and nystagmus. This disorder has been shown to be associated with CNGA3, CNGB3, and GNAT2 mutations, and the frequency of mutations in the CNGA3 gene (encoding α subunit of the cone-specific cGMP-gated cation channel) was 23–33% in European populations. The aim of this study was to test the hypothesis that CNGA3 mutations are also responsible for congenital achromatopsia in Japanese patients. DNA from venous blood samples from a total of 14 patients from 13 Japanese pedigrees was prepared. Mutation screening of the CNGA3 gene was performed using direct sequencing and PCR-single-strand conformation polymorphism analysis. Compound heterozygous missense mutations (p.R436W and p.L633P, the latter of which was novel) were identified in one patient only, a 22-year-old female. Neither of these two mutations was found in 150 Japanese control individuals. The patient's parents and sister carried one of these mutations each but were not affected. No mutations in the CNGB3 or GNAT2 genes were identified in the patient. Clinically, best-corrected visual acuity was 0.1 in both eyes. No specific findings were obtained in funduscopy. Optical coherence topography revealed a normal foveal thickness but a 20% decrease in parafoveal thickness. Ganzfeld full-field electroretinograms (ERGs) showed normal responses in rod and mixed rod-plus-cone ERGs but no response in cone or 30-Hz flicker ERGs. Spectral sensitivity on a white background revealed a curve with only one peak at around 500 nm, which fits the absorption spectrum of human rhodopsin. L633, conserved among vertebrate orthologs of human CNGA3, is a hydrophobic residue forming part of the carboxy-terminal leucine zipper (CLZ) domain, which is functionally important in the mediation of intracellular interactions. To our knowledge, this is the first report of a Japanese complete achromat with CNGA3 mutations, and of any patient with a missense mutation within the CLZ domain. The outcome suggests low frequency (7%, 1/14) of CNGA3 mutations in Japanese patients.

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Identification of a Novel CLRN1 Gene Mutation in Usher Syndrome Type 3

Annals of Otology Rhinology & Laryngology ◽

10.1177/0003489415574069 ◽

2015 ◽

Vol 124 (1_suppl) ◽

pp. 94S-99S ◽

Cited By ~ 2

Author(s):

Hidekane Yoshimura ◽

Chie Oshikawa ◽

Jun Nakayama ◽

Hideaki Moteki ◽

Shin-ichi Usami

Keyword(s):

Gene Mutation ◽

Mutation Screening ◽

Usher Syndrome ◽

Japanese Patients ◽

Pathogenic Mutation ◽

Clinical Findings ◽

Syndrome Type ◽

Asian Populations ◽

Type 3 ◽

Usher Syndrome Type

Objective: This study examines the CLRN1 gene mutation analysis in Japanese patients who were diagnosed with Usher syndrome type 3 (USH3) on the basis of clinical findings. Methods: Genetic analysis using massively parallel DNA sequencing (MPS) was conducted to search for 9 causative USH genes in 2 USH3 patients. Results: We identified the novel pathogenic mutation in the CLRN1 gene in 2 patients. The missense mutation was confirmed by functional prediction software and segregation analysis. Both patients were diagnosed as having USH3 caused by the CLRN1 gene mutation. Conclusion: This is the first report of USH3 with a CLRN1 gene mutation in Asian populations. Validating the presence of clinical findings is imperative for properly differentiating among USH subtypes. In addition, mutation screening using MPS enables the identification of causative mutations in USH. The clinical diagnosis of this phenotypically variable disease can then be confirmed.

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High-throughput Single-strand Conformation Polymorphism Analysis of an LPL Gene Mutation by Temperature-controlled On-chip Capillary Electrophoresis

2006 International Conference on Microtechnologies in Medicine and Biology ◽

10.1109/mmb.2006.251527 ◽

2006 ◽

Author(s):

Koichi Ono ◽

Mitsuyasu Koike ◽

Takuhito Ohse ◽

Atsuko Takagi ◽

Yasuyuki Ikeda

Keyword(s):

Capillary Electrophoresis ◽

Gene Mutation ◽

High Throughput ◽

Single Strand Conformation Polymorphism ◽

Polymorphism Analysis ◽

Lpl Gene ◽

Conformation Polymorphism Analysis ◽

Temperature Controlled ◽

On Chip ◽

Conformation Polymorphism

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Molecular study of eight Japanese cases of glucose-6-phosphate dehydrogenase deficiency by nonradioisotopic single-strand conformation polymorphism analysis [see comments]

Blood ◽

10.1182/blood.v83.11.3363.3363 ◽

1994 ◽

Vol 83 (11) ◽

pp. 3363-3368 ◽

Cited By ~ 29

Author(s):

A Hirono ◽

S Miwa ◽

H Fujii ◽

F Ishida ◽

K Yamada ◽

...

Keyword(s):

Direct Sequencing ◽

Japanese Patients ◽

Single Strand Conformation Polymorphism ◽

Single Strand ◽

Sscp Analysis ◽

Polymorphism Analysis ◽

Missense Mutations ◽

G6pd Gene ◽

Glucose 6 Phosphate Dehydrogenase ◽

Conformation Polymorphism

Abstract Using a newly developed nonradioisotopic method of polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) analysis combined with the direct sequencing using the fluorescence-labeled terminator, we identified seven missense mutations, 527 A-->G, 1003 G-- >A, 1159 C--eT, 1160 G-->A, 1229 G-->A, 1246 G-->A, and 1361 G-->A, in eight Japanese patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Except for the 527 A-->G, each mutation has been reported to cause variants G6PD Chatham, G6PD Guadalajara, G6PD Beverly Hills, G6PD “Japan”, G6PD Tokyo, and G6PD Andalus, respectively. In addition, a single base deletion in intron 5 was found in the patients with G6PD Guadalajara or G6PD Andalus. The variant with unique 527 A-->G was characterized and designated as G6PD Shinshu. We also characterized G6PD “Japan” and found that the variant had the striking resemblance with G6PD Riverside, bearing a missense mutation in the same codon, but causing a different amino acid substitution. Our modified PCR-SSCP analysis using minigel and ethidium bromide staining could detect six of the eight diverse mutations in the G6PD gene. Because it is easy and requires no special apparatus, this modified method will be useful for screening mutations in the G6PD gene.

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