Purohit Abhishek, Singh Kuldeep, Kalla Anand Raj, Bohra Manju, Kumar Mayank, Saini Shashikant
Department of Pathology, All India Institute of Medical Sciences, Jodhpur, Rajasthan India.
Department of Paediatrics, All India Institute of Medical Sciences, Jodhpur, Rajasthan India.
Indian J Hematol Blood Transfus. 2021 Oct;37(4):684-688. doi: 10.1007/s12288-021-01414-z. Epub 2021 Feb 22.
β-Thalassaemia, the most common monogenic disorder, is characterized by genetic heterogeneity at the molecular level. More than 300 mutations of the β globin gene have been characterized all over the world, however, few common mutations account for majority of the cases in various populations. The present study aimed to screen known cases of β-thalassaemia in the Western part of Rajasthan state for five common mutations. The study included 144 known cases of β-thalassaemia of all clinical phenotypes. Cases were diagnosed based on clinical features, haematology investigations including haemogram and Hb-HPLC. Blood samples from cases were taken for mutation analysis. After DNA extraction, mutations were characterized by the polymerase chain reaction method employing allele specific priming technique (AMRS) to study the five mutations including IVS-I-5 (G → C), IVS-I-1 (G → T), CD41/42 (-TCTT), CD 8/9 (+G) and 619 bp deletion from the 3' end of the β-globin gene using a total of seven different primers. Of all 144 cases, 74 (51.38% of all) cases were of β-thalassaemia major, five (3.4% of all) cases were of β-thalassaemia intermedia and 65 (45.14% of all) cases were of β-thalassaemia minor. Mutation analysis revealed that five common mutations were present in 130 (90.27% of all) cases. Among identified mutations, highest frequency of mutation was of IVS-I-5 (G → C) identified in 73 cases (50.7% of all cases). In 11 (7.63% of all) cases, more than one mutation was identified. β-Thalassaemias are common in Western Rajasthan; however, there is dearth of literature from this part of the country. We observed that five common mutations are common in this part of the country also. These observations are helping us in forming the basis for comprehensive diagnostic database that would not only be useful for genetic counselling but also for prenatal diagnosis.
β地中海贫血是最常见的单基因疾病,其特征在于分子水平上的遗传异质性。全世界已鉴定出300多种β珠蛋白基因突变,然而,少数常见突变占不同人群中大多数病例。本研究旨在筛查拉贾斯坦邦西部已知的β地中海贫血病例中的五种常见突变。该研究纳入了144例所有临床表型的已知β地中海贫血病例。病例根据临床特征、血液学检查(包括血常规和血红蛋白高效液相色谱分析)进行诊断。采集病例的血样进行突变分析。DNA提取后,采用等位基因特异性引物技术(AMRS)的聚合酶链反应方法对突变进行鉴定,以研究包括IVS-I-5(G→C)、IVS-I-1(G→T)、CD41/42(-TCTT)、CD 8/9(+G)和β珠蛋白基因3'端619 bp缺失在内的五种突变,共使用七种不同引物。在所有144例病例中,74例(占所有病例的51.38%)为重型β地中海贫血,5例(占所有病例的3.4%)为中间型β地中海贫血,65例(占所有病例的45.14%)为轻型β地中海贫血。突变分析显示,130例(占所有病例的90.27%)存在五种常见突变。在已鉴定的突变中,IVS-I-5(G→C)突变频率最高,在73例病例中被鉴定出(占所有病例的50.7%)。在11例(占所有病例的7.63%)病例中,鉴定出不止一种突变。β地中海贫血在拉贾斯坦邦西部很常见;然而,该国这一地区的文献匮乏。我们观察到这五种常见突变在该国这一地区也很常见。这些观察结果有助于我们建立综合诊断数据库,这不仅对遗传咨询有用,而且对产前诊断也有用。