Mol. Hum. Reprod. Advance Access published online on September 14, 2006
Molecular Human Reproduction, doi:10.1093/molehr/gal077
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Reproductive Genetics, Reproductive Biomedicine Research Center of Royan Institute, Tehran, Iran
* To whom correspondence should be addressed. Congenital bilateral absence of the vas deferens (CBAVD) is a frequent cause of obstructive azoospermia. Nearly 75% of men with CBAVD have at least one detectable common cystic fibrosis (CF) transmembrane conductance regulator (CFTR) mutation. To study the involvement of CFTR mutations in the Iranian population with presumed low CF frequency, we analysed 112 Iranian CBAVD males. Three Iranian CBAVD males with no clinical CF phenotype indicated by a normal karyotype, normal pancreatic function and sweat chloride concentration and no Y chromosome microdeletions were studied for CFTR mutations, IVS8-5T mutations and M470V exon 10 missense polymorphism. The entire coding sequence of each gene was analysed using a combination of the denaturing gradient-gel electrophoresis or by single-strand conformation analysis and direct DNA sequencing. Also, 52 fertile males were tested as controls to rule out polymorphism. This approach allowed us to detect one novel nonsense mutation (K536X) in the nucleotide-binding domain 1 (NBD1) region and two novel missense mutations (Y122H and T338A) in the M2 and M6 regions of CFTR gene in our studied population, which were not reported previously. Also, the conservation of changed nucleotide and amino acid in mutated regions was analysed by aligning with nine different species. K536X nonsense mutation (transversion) was found in the first NBD (NBF1), which plays an important regulatory role in CFTR function. It was, therefore, considered as a severe allele responsible for elevated sweat chloride levels and obstructive azoospermia. Because Y122H and T338A mutations were compound heterozygote with the IVS8-5T, it is difficult to judge the severity of these mutations and their role in the CBAVD phenotype.
Received May 22, 2006
Revised June 28, 2006
Accepted August 15, 2006
Article
Two novel missense and one novel nonsense CFTR mutations in Iranian males with congenital bilateral absence of the vas deferens
Ramin Radpour 1 *, Hamid Gourabi 1, Mohamad A. Sadighi Gilani 2, Ahmad Vosough Dizaj 2, Mina Rezaee 3, and Sepideh Mollamohamadi 4
2 Department of Male Infertility, Reproductive Biomedicine Research Center of Royan Institute, Tehran, Iran
3 Genetic Research Center of Social Welfare and Rehabilitation Sciences University, Tehran, Iran
4 Department of Stem Cell, Reproductive Biomedicine Research Center of Royan Institute, Tehran, Iran
Ramin Radpour, E-mail: rradpour{at}royaninstitute.org
Abstract 
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  R. Radpour, H. Gourabi, A. V. Dizaj, W. Holzgreve, and X. Y. Zhong Genetic Investigations of CFTR Mutations in Congenital Absence of Vas Deferens, Uterus, and Vagina as a Cause of Infertility J Androl, September 1, 2008; 29(5): 506 - 513. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Radpour, H. Gourabi, M. A. S. Gilani, and A. V. Dizaj Correlation Between CFTR Gene Mutations in Iranian Men With Congenital Absence of the Vas Deferens and Anatomical Genital Phenotype J Androl, January 1, 2008; 29(1): 35 - 40. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Radpour, H. Gourabi, M. A. S. Gilani, and A. V. Dizaj Molecular Study of (TG)m(T)n Polymorphisms in Iranian Males With Congenital Bilateral Absence of the Vas Deferens J Androl, July 1, 2007; 28(4): 541 - 547. [Abstract] [Full Text] [PDF]
|
|