Ansari Saqib H, Shamsi Tahir S, Ashraf Mushtaq, Bohray Muneera, Farzana Tasneem, Khan Mohammed Tahir, Perveen Kousar, Erum Sajida, Ansari Iqra, Nadeem Muhammad, Ahmed Masood, Raza Faizan
Department of Pediatric Hematology & Molecular Medicine, National Institute of Blood Diseases Karachi, Pakistan.
Int J Mol Epidemiol Genet. 2011;2(4):403-8. Epub 2011 Nov 28.
β-thalassaemia, an autosomal recessive hemoglobinopathy, is one of the commonest genetically transmitted disorders throughout the world. Collective measures including carrier identification, genetic counseling and prenatal diagnosis are required for preventing β-thalassemia. To achieve this objective, Identification of the spectrum of genetic mutations, especially for various ethnic backgrounds in Pakistan is necessary. Therefore, we designed a cross sectional prospective study to identify the frequency of various gene mutations in different ethnic groups of Pakistan. Over a 5-year period, DNA from 648 blood samples [including specimens of chorionic villus sampling (CVS)] were analyzed for the twelve most common β-thalassemia mutations found in the Pakistani population by a Multiplex amplification refractory mutation system (ARMS). The most common mutation identified was Intervening Sequence 1-5 (IVS 1-5 (G-C)); accounting for 40.89% mutated alleles, and was represented in all ethnic groups. 15.7 % of the β-thalassemia alleles were found to have Frameshift 8-9 (Fr 8-9) as the second most common mutation Other common genetic defects responsible for β-thalassemia: IVS 1-1 (G-T) was found in 8.17%, Codon-30 (Cd-30 (G-C)) 8.02%, Codon-5(Cd-5 (-CT)) contributed 2.16% and Deletion 619 base pair (Del 619bp) affected 11.11% were found in Pakistan. This large study adds to the pre-existing data in Pakistan. Knowledge of the predominant mutation in a given ethnic group will not only help in developing a short panel of (population-specific) primers of mutations thereby providing a cost-effective method for prenatal diagnosis and also help the clinicians to counsel regarding blood transfusion regimen/ pregnancy termination.
β地中海贫血是一种常染色体隐性血红蛋白病，是全球最常见的遗传疾病之一。预防β地中海贫血需要采取包括携带者鉴定、遗传咨询和产前诊断在内的综合措施。为实现这一目标，有必要确定基因突变谱，特别是针对巴基斯坦不同种族背景的人群。因此，我们设计了一项横断面前瞻性研究，以确定巴基斯坦不同种族群体中各种基因突变的频率。在5年的时间里，我们通过多重扩增不应性突变系统（ARMS）对648份血样（包括绒毛取样标本）的DNA进行分析，以检测巴基斯坦人群中发现的12种最常见的β地中海贫血突变。鉴定出的最常见突变是内含子序列1-5（IVS 1-5（G-C））；占突变等位基因的40.89%，在所有种族群体中均有出现。15.7%的β地中海贫血等位基因被发现具有移码8-9（Fr 8-9）作为第二常见突变。其他导致β地中海贫血的常见遗传缺陷：IVS 1-1（G-T）占8.17%，密码子30（Cd-30（G-C））占8.02%，密码子5（Cd-5（-CT））占2.16%，619碱基对缺失（Del 619bp）占11.11%，这些在巴基斯坦均有发现。这项大型研究增加了巴基斯坦现有的数据。了解特定种族群体中的主要突变不仅有助于开发一套简短的（针对特定人群的）突变引物，从而提供一种经济高效的产前诊断方法，还能帮助临床医生就输血方案/终止妊娠提供咨询。
