Sharma N, Acharya N, Singh S K, Singh M, Sharma U, Prasad R
Department of Biochemistry, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India.
Hum Reprod. 2009 May;24(5):1229-36. doi: 10.1093/humrep/den500. Epub 2009 Jan 30.
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.
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.
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.
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.
囊性纤维化跨膜传导调节因子（CFTR）基因突变可导致先天性双侧输精管缺如。然而，印度男性先天性输精管缺如（CAVD）患者中CFTR基因突变的谱型和频率尚不清楚。
我们对50名在昌迪加尔的PGIMER被诊断为单侧或双侧输精管缺如的印度男性进行了研究，通过单链构象多态性分析随后进行序列分析，以检测最常见的CFTR基因突变以及未知突变。
本研究在100条印度CAVD染色体中的48%上鉴定出12种CFTR基因突变。11名患者（22%）的两个等位基因均检测到CFTR突变，26名患者（52%）的一个等位基因检测到CFTR突变。鉴定出的新CFTR突变有L69H、F87I、G126S、F157C、E543A、Y852F和D1270E。最常见的突变是T5等位基因（25%）和F508del（11%）。F508del最常见的基因内标记单倍型是2111（GATT、TUB9、M470V和T854T）。13名CAVD患者（26%）未检测到突变，其中4名伴有肾脏畸形。
本研究证实了CAVD中CFTR基因突变的分子异质性。虽然印度CAVD患者的突变检出率确实较低，但74%的受试患者至少有一个CFTR基因突变。未检测到突变的CAVD等位基因表明，其他变化可能位于未筛查的位点，需要通过直接测序进行广泛搜索。此外，鉴定出的新CFTR突变需要在基于细胞的系统中进行功能研究。
