Micropenis and the 5α-reductase-2 (SRD5A2) gene: Mutation and V89L polymorphism analysis in 81 Japanese patients

Goro Sasaki, Tsutomu Ogata, Tomohiro Ishii, Kenjiro Kosaki, Seiji Sato, Keiko Homma, Takao Takahashi, Tomonobu Hasegawa, Nobutake Matsuo

研究成果: Article

46 引用 (Scopus)

抄録

The 5α-reductase-2 encoded by the SRD5A2 gene plays a critical role in male sex differentiation by converting testosterone into 5α dihydrotestosterone in the peripheral target tissues. In this study, we examined the SRD5A2 gene in 81 Japanese patients with micropenis (age, 0-14 yr; median, 7 yr) whose stretched penile lengths were between -2.5 SD and -2.0 so in 39 patients (age, 0-13 yr; median, 8 yr) and below -2.5 SD in 42 patients (age, 0-14 yr; median, 6 yr), together with 100 control males (50 boys and 50 fertile adult males). Mutation analysis was performed for exons 1-5 and their flanking introns by denaturing HPLC and direct sequencing, revealing Y26X/R227Q in an 11-yr-old boy with a penile length of -2.6 SD, G34R/R227Q in a 9-yr-old boy with a penile length of -3.6 SD, and R227Q/R227Q in a 3-yr-old boy with a penile length of -2.4 SD, together with heterozygous R227Q in a control boy and a fertile adult male. Polymorphism analysis was carried out for the most frequent V89L known to reduce the enzyme activity by approximately 30% in 78 patients, except for the three patients with SRD5A2 mutations, and in the 100 control males by direct sequencing, showing that allele and genotype frequencies were similar between 78 patients with micropenis below -2.0 SD or 40 patients with micropenis below -2.5 SD and the 100 control males, the 50 boys, or the 50 fertile adult males, with no statistically significant differences. The results suggest that, in Japanese patients, micropenis can be caused by SRD5A2 gene mutations, especially by R227Q which has been shown to retain approximately 3.2% of normal enzyme activity and appears relatively frequent in Asian populations, and that V89L polymorphism is unlikely to raise the susceptibility to the development of micropenis.

元の言語English
ページ(範囲)3431-3436
ページ数6
ジャーナルJournal of Clinical Endocrinology and Metabolism
88
発行部数7
DOI
出版物ステータスPublished - 2003 7 1

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Polymorphism
Oxidoreductases
Genes
Mutation
Enzyme activity
Dihydrotestosterone
Introns
Testosterone
Exons
Tissue
Sex Differentiation
Penis agenesis
Enzymes
Gene Frequency
Genotype
High Pressure Liquid Chromatography
Population

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

これを引用

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title = "Micropenis and the 5α-reductase-2 (SRD5A2) gene: Mutation and V89L polymorphism analysis in 81 Japanese patients",
abstract = "The 5α-reductase-2 encoded by the SRD5A2 gene plays a critical role in male sex differentiation by converting testosterone into 5α dihydrotestosterone in the peripheral target tissues. In this study, we examined the SRD5A2 gene in 81 Japanese patients with micropenis (age, 0-14 yr; median, 7 yr) whose stretched penile lengths were between -2.5 SD and -2.0 so in 39 patients (age, 0-13 yr; median, 8 yr) and below -2.5 SD in 42 patients (age, 0-14 yr; median, 6 yr), together with 100 control males (50 boys and 50 fertile adult males). Mutation analysis was performed for exons 1-5 and their flanking introns by denaturing HPLC and direct sequencing, revealing Y26X/R227Q in an 11-yr-old boy with a penile length of -2.6 SD, G34R/R227Q in a 9-yr-old boy with a penile length of -3.6 SD, and R227Q/R227Q in a 3-yr-old boy with a penile length of -2.4 SD, together with heterozygous R227Q in a control boy and a fertile adult male. Polymorphism analysis was carried out for the most frequent V89L known to reduce the enzyme activity by approximately 30{\%} in 78 patients, except for the three patients with SRD5A2 mutations, and in the 100 control males by direct sequencing, showing that allele and genotype frequencies were similar between 78 patients with micropenis below -2.0 SD or 40 patients with micropenis below -2.5 SD and the 100 control males, the 50 boys, or the 50 fertile adult males, with no statistically significant differences. The results suggest that, in Japanese patients, micropenis can be caused by SRD5A2 gene mutations, especially by R227Q which has been shown to retain approximately 3.2{\%} of normal enzyme activity and appears relatively frequent in Asian populations, and that V89L polymorphism is unlikely to raise the susceptibility to the development of micropenis.",
author = "Goro Sasaki and Tsutomu Ogata and Tomohiro Ishii and Kenjiro Kosaki and Seiji Sato and Keiko Homma and Takao Takahashi and Tomonobu Hasegawa and Nobutake Matsuo",
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T1 - Micropenis and the 5α-reductase-2 (SRD5A2) gene

T2 - Mutation and V89L polymorphism analysis in 81 Japanese patients

AU - Sasaki, Goro

AU - Ogata, Tsutomu

AU - Ishii, Tomohiro

AU - Kosaki, Kenjiro

AU - Sato, Seiji

AU - Homma, Keiko

AU - Takahashi, Takao

AU - Hasegawa, Tomonobu

AU - Matsuo, Nobutake

PY - 2003/7/1

Y1 - 2003/7/1

N2 - The 5α-reductase-2 encoded by the SRD5A2 gene plays a critical role in male sex differentiation by converting testosterone into 5α dihydrotestosterone in the peripheral target tissues. In this study, we examined the SRD5A2 gene in 81 Japanese patients with micropenis (age, 0-14 yr; median, 7 yr) whose stretched penile lengths were between -2.5 SD and -2.0 so in 39 patients (age, 0-13 yr; median, 8 yr) and below -2.5 SD in 42 patients (age, 0-14 yr; median, 6 yr), together with 100 control males (50 boys and 50 fertile adult males). Mutation analysis was performed for exons 1-5 and their flanking introns by denaturing HPLC and direct sequencing, revealing Y26X/R227Q in an 11-yr-old boy with a penile length of -2.6 SD, G34R/R227Q in a 9-yr-old boy with a penile length of -3.6 SD, and R227Q/R227Q in a 3-yr-old boy with a penile length of -2.4 SD, together with heterozygous R227Q in a control boy and a fertile adult male. Polymorphism analysis was carried out for the most frequent V89L known to reduce the enzyme activity by approximately 30% in 78 patients, except for the three patients with SRD5A2 mutations, and in the 100 control males by direct sequencing, showing that allele and genotype frequencies were similar between 78 patients with micropenis below -2.0 SD or 40 patients with micropenis below -2.5 SD and the 100 control males, the 50 boys, or the 50 fertile adult males, with no statistically significant differences. The results suggest that, in Japanese patients, micropenis can be caused by SRD5A2 gene mutations, especially by R227Q which has been shown to retain approximately 3.2% of normal enzyme activity and appears relatively frequent in Asian populations, and that V89L polymorphism is unlikely to raise the susceptibility to the development of micropenis.

AB - The 5α-reductase-2 encoded by the SRD5A2 gene plays a critical role in male sex differentiation by converting testosterone into 5α dihydrotestosterone in the peripheral target tissues. In this study, we examined the SRD5A2 gene in 81 Japanese patients with micropenis (age, 0-14 yr; median, 7 yr) whose stretched penile lengths were between -2.5 SD and -2.0 so in 39 patients (age, 0-13 yr; median, 8 yr) and below -2.5 SD in 42 patients (age, 0-14 yr; median, 6 yr), together with 100 control males (50 boys and 50 fertile adult males). Mutation analysis was performed for exons 1-5 and their flanking introns by denaturing HPLC and direct sequencing, revealing Y26X/R227Q in an 11-yr-old boy with a penile length of -2.6 SD, G34R/R227Q in a 9-yr-old boy with a penile length of -3.6 SD, and R227Q/R227Q in a 3-yr-old boy with a penile length of -2.4 SD, together with heterozygous R227Q in a control boy and a fertile adult male. Polymorphism analysis was carried out for the most frequent V89L known to reduce the enzyme activity by approximately 30% in 78 patients, except for the three patients with SRD5A2 mutations, and in the 100 control males by direct sequencing, showing that allele and genotype frequencies were similar between 78 patients with micropenis below -2.0 SD or 40 patients with micropenis below -2.5 SD and the 100 control males, the 50 boys, or the 50 fertile adult males, with no statistically significant differences. The results suggest that, in Japanese patients, micropenis can be caused by SRD5A2 gene mutations, especially by R227Q which has been shown to retain approximately 3.2% of normal enzyme activity and appears relatively frequent in Asian populations, and that V89L polymorphism is unlikely to raise the susceptibility to the development of micropenis.

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