Hum. Reprod. Advance Access originally published online on January 30, 2009
Human Reproduction 2009 24(5):1229-1236; doi:10.1093/humrep/den500
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Heterogenous spectrum of CFTR gene mutations in Indian patients with congenital absence of vas deferens
1 Department of Biochemistry, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India 2 Department of Urology, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India 3 Department of Pediatrics, Advanced Pediatric Centre, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India
4 Correspondence address. Tel: +91 172-2755178; Fax: +91-172-2744401/2745078; E-mail: fateh1977{at}yahoo.com
BACKGROUND: Mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene can cause congenital bilateral absence of vas deferens. Yet, the spectrum and frequency of CFTR mutations in Indian males with congenital absence of vas deferens (CAVD) is unknown.
METHODS: We investigated 50 Indian males, diagnosed with unilateral or bilateral absence of vas deferens at the PGIMER, Chandigarh, for the presence of the most common CFTR gene mutations as well as unknown mutations by single-strand conformation polymorphism followed by sequence analysis.
RESULTS: This study led to the identification of 12 CFTR gene mutations on 48% of 100 Indian CAVD chromosomes. CFTR mutations were identified on both alleles in 11 patients (22%) and on one allele in 26 patients (52%). Novel CFTR mutations identified were L69H, F87I, G126S, F157C, E543A, Y852F and D1270E. The T5 allele (25%) and F508del (11%) were the most common mutations identified. The most common intragenic marker haplotype for F508del was 2111 (GATT, TUB9, M470V and T854T). No mutations could be detected in 13 CAVD patients (26%), including 4 with renal malformations.
CONCLUSIONS: This study confirms the molecular heterogeneity of CFTR mutations in CAVD. Although the mutation detection rate is indeed lower in Indian CAVD patients, 74% of the patients tested had at least one CFTR mutation. CAVD alleles with no mutations suggest that other changes may be located at the non-screened sites that require extensive search by direct sequencing. Furthermore, the novel CFTR mutations identified require functional studies in a cell-based system.
Key words: congenital absence of vas deferens/cystic fibrosis/CFTR/F508del/single-strand conformational polymorphism
Submitted on September 12, 2008; resubmitted on December 16, 2008; accepted on December 28, 2008.