title: Distribution of beta-thalassemia mutations in the Indian population referred to a diagnostic center.
abstract: 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.
authors.affiliation: Department of Molecular Biology, Bai Jerbai Wadia Hospital for Children and Institute of Child Health Research Society, Parel, Bombay.
authors.forename: F E
authors.initials: FE
authors.lastname: Vaz
authors.forename: C B
authors.initials: CB
authors.lastname: Thakur
authors.forename: M K
authors.initials: MK
authors.lastname: Banerjee
authors.forename: S G
authors.initials: SG
authors.lastname: Gangal
mesh_terms: D000483:Alleles; D004252:DNA Mutational Analysis; D005006:Ethnicity / Q000235:genetics; D005192:Family Health; D016368:Frameshift Mutation; D005787:Gene Frequency; D005820:Genetic Testing; D006446:Hemoglobin E / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D007194:India / Q000453:epidemiology; D009154:Mutation / Q000235:genetics; D017354:Point Mutation; D017086:beta-Thalassemia / Q000453:epidemiology / Q000235:genetics*
chemical_list: D006446:Hemoglobin E