Mutation spectrum of the CFTR gene in Taiwanese patients with congenital bilateral absence of the vas deferens

Chien Chih Wu, Özgül M. Alper, Jyh Feng Lu, Song Ping Wang, Li Guo, Han-Sun Chiang, Lee Jun C Wong

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Abstract

Background: Clinically affected cystic fibrosis (CF) patients present a spectrum of genital phenotypes ranging from normal fertility to moderately impaired spermatogenesis and congenital bilateral absence of vas deferens (CBAVD). Little is known about the CF incidence in the Taiwanese population. It has been shown that the CBAVD in men without clinical evidence of CF is associated with a high incidence of mutated CFTR (cystic fibrosis transmembrane conductance regulator) alleles. In order to understand the involvement of the CFTR gene in the aetiology of Asian/Taiwanese male infertility, we screened the entirety of the CFTR gene in 36 infertile males with CBAVD. Methods: Temporal temperature gradient gel electrophoresis (TTGE) followed by direct DNA sequencing was used. Results: Five mutations, p.V201M, p.N287K, c.-8G>C (125G>C), p.M469I and p.S895N, were found in five of the patients. p.N287K occurred in the first transmembrane-spanning domain, p.M469I in the first ATP-binding domain and p.S895N in the second transmembrane-spanning domain, were novel. In addition, seven homozygous and seven heterozygous 5T alleles in the intron 8 poly(T) tract were found. The overall frequency of CFTR mutant alleles in Taiwanese CBAVD males was 26 out of 72=36%. This finding was lower than the published frequency of CFTR mutations in other ethnic CBAVD patients (ranging from 50 to 74%). The frequency of p.M470V in Taiwanese CBAVD patients is not significantly different from that in the general population P=0.12). Conclusions: The results of this study add to the short list of Taiwanese/Asian CFTR mutations. Unlike Caucasian patients, the CFTR mutations cannot account for the majority of Taiwanese CBAVD. This is consistent with the low incidence of CF in the Asian/Taiwanese population. Furthermore, the mutation spectrum of CFTR in CBAVD patients does not overlap with the Caucasian CFTR mutation spectrum.

Original languageEnglish
Pages (from-to)2470-2475
Number of pages6
JournalHuman Reproduction
Volume20
Issue number9
DOIs
Publication statusPublished - Sep 2005

Fingerprint

Cystic Fibrosis Transmembrane Conductance Regulator
Regulator Genes
Mutation
Cystic Fibrosis
Alleles
Incidence
Poly T
Population
Congenital bilateral aplasia of vas deferens
Denaturing Gradient Gel Electrophoresis
Male Infertility
Spermatogenesis
DNA Sequence Analysis
Introns
Fertility
Adenosine Triphosphate
Phenotype

Keywords

  • CBAVD
  • CFTR
  • IVS8-5T
  • Male infertility
  • Taiwanese CF

ASJC Scopus subject areas

  • Physiology
  • Developmental Biology
  • Obstetrics and Gynaecology
  • Reproductive Medicine

Cite this

Mutation spectrum of the CFTR gene in Taiwanese patients with congenital bilateral absence of the vas deferens. / Wu, Chien Chih; Alper, Özgül M.; Lu, Jyh Feng; Wang, Song Ping; Guo, Li; Chiang, Han-Sun; Wong, Lee Jun C.

In: Human Reproduction, Vol. 20, No. 9, 09.2005, p. 2470-2475.

Research output: Contribution to journalArticle

Wu, Chien Chih ; Alper, Özgül M. ; Lu, Jyh Feng ; Wang, Song Ping ; Guo, Li ; Chiang, Han-Sun ; Wong, Lee Jun C. / Mutation spectrum of the CFTR gene in Taiwanese patients with congenital bilateral absence of the vas deferens. In: Human Reproduction. 2005 ; Vol. 20, No. 9. pp. 2470-2475.
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abstract = "Background: Clinically affected cystic fibrosis (CF) patients present a spectrum of genital phenotypes ranging from normal fertility to moderately impaired spermatogenesis and congenital bilateral absence of vas deferens (CBAVD). Little is known about the CF incidence in the Taiwanese population. It has been shown that the CBAVD in men without clinical evidence of CF is associated with a high incidence of mutated CFTR (cystic fibrosis transmembrane conductance regulator) alleles. In order to understand the involvement of the CFTR gene in the aetiology of Asian/Taiwanese male infertility, we screened the entirety of the CFTR gene in 36 infertile males with CBAVD. Methods: Temporal temperature gradient gel electrophoresis (TTGE) followed by direct DNA sequencing was used. Results: Five mutations, p.V201M, p.N287K, c.-8G>C (125G>C), p.M469I and p.S895N, were found in five of the patients. p.N287K occurred in the first transmembrane-spanning domain, p.M469I in the first ATP-binding domain and p.S895N in the second transmembrane-spanning domain, were novel. In addition, seven homozygous and seven heterozygous 5T alleles in the intron 8 poly(T) tract were found. The overall frequency of CFTR mutant alleles in Taiwanese CBAVD males was 26 out of 72=36{\%}. This finding was lower than the published frequency of CFTR mutations in other ethnic CBAVD patients (ranging from 50 to 74{\%}). The frequency of p.M470V in Taiwanese CBAVD patients is not significantly different from that in the general population P=0.12). Conclusions: The results of this study add to the short list of Taiwanese/Asian CFTR mutations. Unlike Caucasian patients, the CFTR mutations cannot account for the majority of Taiwanese CBAVD. This is consistent with the low incidence of CF in the Asian/Taiwanese population. Furthermore, the mutation spectrum of CFTR in CBAVD patients does not overlap with the Caucasian CFTR mutation spectrum.",
keywords = "CBAVD, CFTR, IVS8-5T, Male infertility, Taiwanese CF",
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AU - Wu, Chien Chih

AU - Alper, Özgül M.

AU - Lu, Jyh Feng

AU - Wang, Song Ping

AU - Guo, Li

AU - Chiang, Han-Sun

AU - Wong, Lee Jun C

PY - 2005/9

Y1 - 2005/9

N2 - Background: Clinically affected cystic fibrosis (CF) patients present a spectrum of genital phenotypes ranging from normal fertility to moderately impaired spermatogenesis and congenital bilateral absence of vas deferens (CBAVD). Little is known about the CF incidence in the Taiwanese population. It has been shown that the CBAVD in men without clinical evidence of CF is associated with a high incidence of mutated CFTR (cystic fibrosis transmembrane conductance regulator) alleles. In order to understand the involvement of the CFTR gene in the aetiology of Asian/Taiwanese male infertility, we screened the entirety of the CFTR gene in 36 infertile males with CBAVD. Methods: Temporal temperature gradient gel electrophoresis (TTGE) followed by direct DNA sequencing was used. Results: Five mutations, p.V201M, p.N287K, c.-8G>C (125G>C), p.M469I and p.S895N, were found in five of the patients. p.N287K occurred in the first transmembrane-spanning domain, p.M469I in the first ATP-binding domain and p.S895N in the second transmembrane-spanning domain, were novel. In addition, seven homozygous and seven heterozygous 5T alleles in the intron 8 poly(T) tract were found. The overall frequency of CFTR mutant alleles in Taiwanese CBAVD males was 26 out of 72=36%. This finding was lower than the published frequency of CFTR mutations in other ethnic CBAVD patients (ranging from 50 to 74%). The frequency of p.M470V in Taiwanese CBAVD patients is not significantly different from that in the general population P=0.12). Conclusions: The results of this study add to the short list of Taiwanese/Asian CFTR mutations. Unlike Caucasian patients, the CFTR mutations cannot account for the majority of Taiwanese CBAVD. This is consistent with the low incidence of CF in the Asian/Taiwanese population. Furthermore, the mutation spectrum of CFTR in CBAVD patients does not overlap with the Caucasian CFTR mutation spectrum.

AB - Background: Clinically affected cystic fibrosis (CF) patients present a spectrum of genital phenotypes ranging from normal fertility to moderately impaired spermatogenesis and congenital bilateral absence of vas deferens (CBAVD). Little is known about the CF incidence in the Taiwanese population. It has been shown that the CBAVD in men without clinical evidence of CF is associated with a high incidence of mutated CFTR (cystic fibrosis transmembrane conductance regulator) alleles. In order to understand the involvement of the CFTR gene in the aetiology of Asian/Taiwanese male infertility, we screened the entirety of the CFTR gene in 36 infertile males with CBAVD. Methods: Temporal temperature gradient gel electrophoresis (TTGE) followed by direct DNA sequencing was used. Results: Five mutations, p.V201M, p.N287K, c.-8G>C (125G>C), p.M469I and p.S895N, were found in five of the patients. p.N287K occurred in the first transmembrane-spanning domain, p.M469I in the first ATP-binding domain and p.S895N in the second transmembrane-spanning domain, were novel. In addition, seven homozygous and seven heterozygous 5T alleles in the intron 8 poly(T) tract were found. The overall frequency of CFTR mutant alleles in Taiwanese CBAVD males was 26 out of 72=36%. This finding was lower than the published frequency of CFTR mutations in other ethnic CBAVD patients (ranging from 50 to 74%). The frequency of p.M470V in Taiwanese CBAVD patients is not significantly different from that in the general population P=0.12). Conclusions: The results of this study add to the short list of Taiwanese/Asian CFTR mutations. Unlike Caucasian patients, the CFTR mutations cannot account for the majority of Taiwanese CBAVD. This is consistent with the low incidence of CF in the Asian/Taiwanese population. Furthermore, the mutation spectrum of CFTR in CBAVD patients does not overlap with the Caucasian CFTR mutation spectrum.

KW - CBAVD

KW - CFTR

KW - IVS8-5T

KW - Male infertility

KW - Taiwanese CF

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