CASE REPORT: Common origin of a rare b-globin initiation codon mutation (ATG1AGG) in Asians

• Published in: Clinical and laboratory haematology Vol. 27; no. 6; pp. 409 - 415
• Main Authors: Viprakasit, V, Chinchang, W, Suwanthol, L, Tanphaichitr, V S
• Format: Journal Article
• Language: English
• Published: 01-12-2005
• ISSN: 0141-9854; 1365-2257
• DOI: 10.1111/j.1365-2257.2005.00734.x

In this report, we describe two Thai siblings presenting with mild hypochromic microcytic anaemia and splenomegaly since 212 years of age. However, both patients were otherwise well with normal weight and height development and did not require transfusion during the 6-year follow-up period. Haematological and haemoglobin analyses were consistent with the clinical diagnosis of Hb E/b-thalassaemia disease. To provide proper genetic counselling for this family, a definitive diagnosis of b-thalassaemia was achieved using molecular analysis. We identified a rare initiation codon mutation (ATG1AGG) of the b-globin gene in combination with the Hb E mutation (codon 26: GAG1AAG). The initiation codon mutation has previously been reported in several East Asian populations but has never been found in Southeast Asia and in combination with Hb E before. The haplotype analysis revealed a common origin of this mutation in the Asian population (5': - + - + + - +: 3', type IV with framework 3 according to Orkin S, et al.). Although this rare mutation abolished the b-globin expression and was considered as b super(0)-thalassaemia, the relatively mild phenotype in our patients may be attributed to a strong association between this mutation and the -158 super(G)g (C1T) polymorphism, an XmnI cleavage site (+), resulting in a high propensity of postnatal g-globin expression and ameliorating the clinical phenotypes.