Gupta Anju, Hattori Yukio, Gupta Usha R, Sarwai Swati, Nigam Nitu, Singhal Pragya, Agarwal Sarita
Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow-226014, India.
Genet Test. 2003 Summer;7(2):163-8. doi: 10.1089/109065703322146894.
Hemoglobinopathies are the most commonly inherited genetic disorders in India. Certain communities in India have a high predisposition to beta-thalassemia. To offer prenatal diagnosis and to prevent the birth of an affected child, mutation testing in clinically diagnosed beta-thalassemia patients/carriers is a prerequisite. Over a period of 4 years, we have conducted DNA analysis in 385 carriers for 15 beta-thalassemia mutations, HbD, HbE, and HbS. Using reverse dot blot (RDB) and amplification refractory mutation system (ARMS), we have been able to identify mutations in 381 of 385 thalassemia chromosomes. The study included the analysis of five common mutations found in Asian Indians, namely IVS1-5 (G-C), 619-bp deletion, IVS1-1 (G-T), and the frameshifts at CD8/9(+G) and CD41/42(-CTTT). The occurrence of these five mutations was seen in 299 (91.2%) carriers referred to us, the percentage of mutations varying between 4.0 and 68.9%. We also found Cd16 (-C) in 2.1%, CD30 (G-C) in 1.5%, and CD 15(G-A) in 0.6%; these are considered common mutations in the Indian population, as well. The beta-thalassemia anomaly in 4 (0.6%) carriers remained uncharacterized by RDB and ARMS analysis. During delineation of the mutations in uncharacterized carriers by single-stranded conformational polymorphism (SSCP) and sequencing analysis, we have also been able to identify two unusual mutations, one involving an initiation codon and the second involving a novel 8-bp deletion, in Indian families of Uttar Pradesh origin.
血红蛋白病是印度最常见的遗传性疾病。印度的某些群体极易患β地中海贫血。为了提供产前诊断并预防患病儿童的出生，对临床诊断的β地中海贫血患者/携带者进行突变检测是一项先决条件。在4年的时间里，我们对385名携带者进行了15种β地中海贫血突变、血红蛋白D（HbD）、血红蛋白E（HbE）和血红蛋白S（HbS）的DNA分析。使用反向点杂交（RDB）和扩增阻滞突变系统（ARMS），我们已经能够在385条地中海贫血染色体中的381条上鉴定出突变。该研究包括对亚洲印度人中发现的五种常见突变的分析，即内含子1-5（G→C）、619bp缺失、内含子1-1（G→T）以及密码子8/9（+G）和密码子41/42（-CTTT）处的移码突变。在转介给我们的299名（91.2%）携带者中发现了这五种突变，突变的百分比在4.0%至68.9%之间变化。我们还发现2.1%的携带者中有密码子16（-C）突变，1.5%的携带者中有密码子30（G→C）突变，0.6%的携带者中有密码子15（G→A）突变；这些突变在印度人群中也被认为是常见突变。4名（0.6%）携带者的β地中海贫血异常通过RDB和ARMS分析仍未得到明确。在通过单链构象多态性（SSCP）和测序分析确定未明确携带者的突变过程中，我们还在来自北方邦的印度家庭中鉴定出了两种不寻常的突变，一种涉及起始密码子，另一种涉及一个新的8bp缺失。
