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An IVS‐I‐117 (G→A) acceptor splice site mutation in the α 1‐globin gene is a nondeletional α‐thalassaemia‐2 determinant in an Indian population
Author(s) -
Clürük M. A.,
Baysal E.,
Gupta R. B.,
Sharma S.,
Huisman T. H. J.
Publication year - 1993
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.1993.tb08658.x
Subject(s) - genetics , rna splicing , mutation , gene , splice , population , splice site mutation , globin , medicine , biology , rna , environmental health
Summary. In 1991 we reported the identification of two deletional α‐thalassaemia‐2 determinants (— 3.7 kb and — 4.2 kb) and one nondeletional α‐thalassaemia‐2 determinant (Hb Koya Dora α2 codon 142 , TAA→TAA) in a tribal population in Central India (Gupta et al, 1991). Evidence was obtained at that time for the possible presence of an additional nondeletional α‐thalassaemia‐2 because of low levels of Hb S (<28%) in some Hb S heterozygotes with a simple α‐thalassaemia‐2 heterozygosity (—α/αα). This abnormality has now been identified as a G→A mutation at IVS‐I‐117 of the α1‐globin gene (acceptor splice site) which makes this gene nonfunctional. Its frequency was established at ˜6% which raises the total frequency of α‐thalassaemia determinants in this population to ˜60%. Subjects with a deletional α‐thalassaemia‐2 and the newly discovered α1 acceptor splice junction mutation in trans appear to have an α chain deficiency similar to that of an α‐thalassaemia‐2 homozygote (—α/—α). An additional change (C→G) at the Cap —4 site was observed in six α1‐ and one α2‐globin genes: this polymorphism is not associated with a decrease in α chain synthesis and is not linked to the IVS‐I‐117 (G→A) mutation.