Vaz F E, Thakur C B, Banerjee M K, Gangal S G
Department of Molecular Biology, Bai Jerbai Wadia Hospital for Children and Institute of Child Health Research Society, Parel, Bombay.
Hemoglobin. 2000 Aug;24(3):181-94. doi: 10.3109/03630260008997526.
Hemoglobinopathies are the most commonly inherited genetic disorders in India. Population screening has identified certain communities in India with high risk of beta-thalassemia, the prevalence of carrier status in some being as high as 17%. Over a period of 6 years we have conducted DNA analysis on 1,233 carriers of 23 beta-thalassemia mutations and Hb E, using the amplification refractory mutation system. The studies included analyses of five common mutations for Asian Indians, namely IVS-I-5 (G-->C), 619 bp deletion, IVS-I-1 (G-->T), and the frameshifts at codons 8/9 (+G) and 41/42 (-TTCT). The occurrence of these was seen in 1,066 (86.45%) of the carriers referred to us, the percentage of mutations varying between 5.03-42.58%. We found codon 15 (TGG-->TAG) in 47 (3.81%) samples which was also considered a common mutation in the Indian population. Rare beta-thalassemia mutations were found in 87 (7.06%) individuals. We have designed five new primers and modified four primers for nine rare mutations. These were seen in nine (0.73%) samples. The beta-thalassemia anomaly in 33 (2.68%) carriers remained uncharacterized. State-wide and community-wide distribution patterns of mutations indicated that IVS-I-5 (G-->C) is the most common beta-thalassemia allele in the Indian population. Sindhis settled in Gujrat, and Maharashtra and Lohanas from Gujrat showed a prevalence of the 619 bp deletion mutation in 49.2 and 45.5% carriers, respectively. High frequency of the IVS-I-1 (G-->T) mutation was also found in Sindhis (25.5%), Punjabi Hindus (34.7%), and Lohanas (31.2%). These studies of mutation patterns in different communities have helped us in the quick identification of beta-thalassemia mutations for prenatal diagnosis.
血红蛋白病是印度最常见的遗传性基因疾病。人群筛查发现印度某些社区患β地中海贫血的风险很高，一些社区的携带者患病率高达17%。在6年的时间里，我们使用扩增阻滞突变系统对1233名携带23种β地中海贫血突变和血红蛋白E的携带者进行了DNA分析。研究包括对亚洲印度人的五种常见突变进行分析，即IVS-I-5（G→C）、619 bp缺失、IVS-I-1（G→T）以及密码子8/9（+G）和41/42（-TTCT）处的移码突变。在转介给我们的1066名（86.45%）携带者中发现了这些突变，突变百分比在5.03%-42.58%之间。我们在47份（3.81%）样本中发现了密码子15（TGG→TAG），这在印度人群中也被认为是一种常见突变。在87名（7.06%）个体中发现了罕见的β地中海贫血突变。我们针对9种罕见突变设计了5种新引物并修改了4种引物。在9份（0.73%）样本中发现了这些突变。33名（2.68%）携带者的β地中海贫血异常情况仍未明确。全邦和全社区的突变分布模式表明，IVS-I-5（G→C）是印度人群中最常见的β地中海贫血等位基因。定居在古吉拉特邦的信德人以及来自古吉拉特邦的马哈拉施特拉人和洛哈纳人分别有49.2%和45.5%的携带者存在619 bp缺失突变。在信德人（25.5%）、旁遮普印度教徒（34.7%）和洛哈纳人（31.2%）中也发现了IVS-I-1（G→T）突变的高频率。这些对不同社区突变模式的研究有助于我们快速鉴定用于产前诊断的β地中海贫血突变。
