title: Regional distribution of beta-thalassemia mutations in India.
abstract: We have characterized the mutations in 1050 carriers of the beta-thalassemia gene and analyzed their regional distribution in India. The majority of beta-thalassemia carriers were migrants from Pakistan and their pattern of mutations differed from the rest. The frequency of the 619-bp deletion was 33.3% among the migrants from Pakistan, 8-17% in the northern states, and less than 5% in the other states. Among non-migrant subjects, the predominant mutation was IVS-I-5 (G-->C), varying from 85% in the southern states and 66-70% in the eastern states to 47-60% in the northern states. The mutation IVS-I-1 (G-->T) was observed at high frequency among the migrants from Pakistan (26.2%), but with very low/zero frequency in the other states. Mutations at codons 8/9 (+G) and codons 41/42 (-CTTT) were distributed in all regions of India with a frequency varying from 3% to 15%. Only eight of 12 published rare mutations were observed in subjects from different parts of India. Mutations of codon 5 (-CT) and codons 47/48 (+ATCT) were found exclusively in migrants from Pakistan, and mutation -88 (C-->T) was detected only in subjects from Punjab, Haryana, and Uttar Pradesh. Using the amplification refractory mutation system technique, mutations were successfully identified in 98.2% of subjects. Overall, 91.8% of the subjects had one of the five commonest mutations [IVS-I-5 (G-->C), 34.1%; 619-bp deletion, 21.0%; IVS-I-1 (G-->T) 15.8%; codons 8/9 (+G), 12.1%, and codons 41/42 (-CTTT), 8.7%], 5.9% of the subjects had a less common mutation, while 1.8% of the carriers remained uncharacterized. The application of this knowledge has helped to successfully establish a program of genetic counselling and prenatal diagnosis of beta-thalassemia in order to reduce the burden of this disease in India.
authors.affiliation: Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India. icverma@giasd101.vsnl.net.in
authors.forename: I C
authors.initials: IC
authors.lastname: Verma
authors.forename: R
authors.initials: R
authors.lastname: Saxena
authors.forename: E
authors.initials: E
authors.lastname: Thomas
authors.forename: P K
authors.initials: PK
authors.lastname: Jain
mesh_terms: D003062:Codon; D005260:Female; D006579:Heterozygote; D006801:Humans; D007194:India; D008297:Male; D009154:Mutation; D010154:Pakistan / Q000208:ethnology; D017354:Point Mutation; D017384:Sequence Deletion; D017086:beta-Thalassemia / Q000235:genetics*
chemical_list: D003062:Codon