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The clinical significance of the spectrum of interactions of CAP+1 (A→C), a silent β‐globin gene mutation, with other β‐thalassemia mutations and globin gene modifiers in north Indians
Author(s) -
Garewal Gurjeewan,
Das Reena,
Awasthi Anshu,
Ahluwalia Jasmina,
Marwaha Ram Kumar
Publication year - 2007
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/j.1600-0609.2007.00958.x
Subject(s) - compound heterozygosity , heterozygote advantage , allele , genetics , thalassemia , genotype , loss of heterozygosity , biology , mutation , beta thalassemia , gene mutation , allele frequency , hemoglobinopathy , globin , gene , microbiology and biotechnology , hemolytic anemia , immunology
Objectives : To assess the clinical significance of the interactions of CAP+1 (A→C), a silent β‐globin gene mutation, with other β‐thalassemia mutations and globin gene modifiers in north Indians. Methods: The clinical phenotypes associated with compound heterozygosity for the CAP+1 (A→C) mutation with other β‐thalassemia mutations, together with the potential effect of the genetic modifiers α‐thalassemia and the Xmn‐ 1 G γ C→T polymorphism were studied in 30 patients. The frequency of the CAP+1 (A→C) polymorphism was determined and an analysis of the red cell indices, HbA 2 levels, iron status, and α‐globin genes was carried out in 35 heterozygotes. Results: Based on an analysis of 1075 β‐thalassemia alleles the CAP+1 (A→C) mutation constituted 3.2% of north Indians. There was a wide spectrum of phenotypic severity in compound heterozygotes; 18 of 30 were transfusion dependent. There was a very high frequency of the −/− genotype of the Xmn‐ 1 G γ polymorphism in compound heterozygotes. Analysis of 35 heterozygotes indicated that approximately half were hematologically normal and therefore genuine ‘silent’ carriers. Conclusions: Compound heterozygotes for CAP+1 (A→C) and other severe β‐thalassemia alleles are phenotypically severe enough to necessitate appropriate therapy and counseling. The unexpected severity of these interactions may be due, in part, to the high frequency of β‐thalassemia alleles associated with the Xmn‐ 1 G γ− allele in Indian populations. It is concluded that the CAP+1 (A→C) mutation can pose serious difficulties in screening and counseling programs in populations in which it occurs at a significant frequency.