Nucleotide -88 (C-T) promoter mutation is a common β-thalassemia mutation in the Jat Sikhs of Punjab, India

Abstract

A study of β-gene mutations in Jat Sikhs, a subcaste of Punjabis, revealed a very high prevalence (46%: 41/88) of the mild β++ promoter region mutation -88 (C-T). Sixteen individuals presenting in homozygous form were clinically mild. Un-transfused patients had characteristic hematological findings: high Hb F (38.1-68.6%, mean 47.4%), high Hb A 2 (5.7-9.8%, mean 6.88%), and the rest had adult hemoglobin. The 19 subjects with compound heterozygosity for -88 (C-T) and another β-gene mutation presented both as thalassemia intermedia (four cases) and as thalassemia major (15 cases). One of the four patients with the milder phenotype had a second mild mutation, CAP+1 (β++). In the other three cases with the milder phenotype, the second mutation was associated with the presence of the Xmnl Gγ polymorphism. Notably, the Xmnl Gγ was negative in all the -88 (C-T) alleles. None of the patients had associated α-thalassemia even in the thalassemia intermedia group. Haplotype analysis of the -88 (C-T) homozygous cases showed a single haplotype (+ - - - - + -) in all but two individuals. This haplotype is distinct from those described in the Africans with homozygous -88 (C-T), suggesting that the mutation in our population occurred independently. © 2005 Wiley-Liss, Inc.