Sharma N, Singh M, Kaur G, Thapa B R, Prasad R
Department of Biochemistry, Post Graduate Institute of Medical Education and Research, Chandigarh, India-160012.
Ann Hum Genet. 2009 Jan;73(1):26-33. doi: 10.1111/j.1469-1809.2008.00477.x. Epub 2008 Sep 8.
Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. This study was performed on Indian CF patients (n = 50) to investigate the spectrum of mutations in the CFTR gene and their association with intragenic and extragenic marker haplotypes. We report identification of 14 previously known and eight novel mutations, namely 3986-3987delC, 876-6del4, 1792InsA, L69H, S158N, Q493L, I530L and E1329Q. The frequency of delta F508 was found to be 27%. Absolute linkage between delta F508 and the KM.19-GATT-TUB9-M470V-T854T haplotype (2-2-1-1-1) predicts a relatively recent appearance of delta F508 in Indian CF patients. Low frequency of delta F508 mutation and detection of eight novel and thirteen rare mutations reflect a heterogeneous spectrum of mutations in Indian CF patients. Failure to detect mutations in 34% of alleles indicates the possible presence of gross deletions involving one or more exons or may indicate the location of the molecular defects in either the noncoding parts of the gene or in the promoter region, which warrants analysis of those regions.
囊性纤维化（CF）是一种常染色体隐性疾病，由囊性纤维化跨膜传导调节因子（CFTR）基因突变引起。本研究对印度囊性纤维化患者（n = 50）进行，以调查CFTR基因的突变谱及其与基因内和基因外标记单倍型的关联。我们报告鉴定出14个先前已知的突变和8个新突变，即3986 - 3987delC、876 - 6del4、1792InsA、L69H、S158N、Q493L、I530L和E1329Q。发现ΔF508的频率为27%。ΔF508与KM.19 - GATT - TUB9 - M470V - T854T单倍型（2 - 2 - 1 - 1 - 1）之间的绝对连锁预示着ΔF508在印度囊性纤维化患者中出现的时间相对较近。ΔF508突变的低频以及8个新突变和13个罕见突变的检测反映了印度囊性纤维化患者中突变谱的异质性。在34%的等位基因中未能检测到突变表明可能存在涉及一个或多个外显子的大片段缺失，或者可能表明分子缺陷位于基因的非编码部分或启动子区域，这需要对这些区域进行分析。
