title: Nucleotide -88 (C-T) promoter mutation is a common beta-thalassemia mutation in the Jat Sikhs of Punjab, India.
abstract: A study of beta-gene mutations in Jat Sikhs, a subcaste of Punjabis, revealed a very high prevalence (46%: 41/88) of the mild beta++ 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 A2 (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 beta-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 (beta++). In the other three cases with the milder phenotype, the second mutation was associated with the presence of the XmnI Ggamma polymorphism. Notably, the XmnI Ggamma was negative in all the -88 (C-T) alleles. None of the patients had associated alpha-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.
authors.affiliation: Department of Haematology, Postgraduate Institute of Medical Education & Research, Chandigarh, India. haemat@eth.net
authors.forename: Gurjeewan
authors.initials: G
authors.lastname: Garewal
authors.forename: Reena
authors.initials: R
authors.lastname: Das
authors.forename: Jasmina
authors.initials: J
authors.lastname: Ahluwalia
authors.forename: R K
authors.initials: RK
authors.lastname: Marwaha
authors.forename: S
authors.initials: S
authors.lastname: Varma
mesh_terms: D000293:Adolescent; D000328:Adult; D001803:Blood Transfusion; D002648:Child; D004247:DNA / Q000032:analysis; D005006:Ethnicity; D005914:Globins / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007194:India; D009154:Mutation; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic; D017086:beta-Thalassemia / Q000097:blood / Q000235:genetics*
chemical_list: D005914:Globins; D004247:DNA