Common origin of a rare beta-globin initiation codon mutation (ATG-->AGG) in Asians.
In this report, we describe two Thai siblings presenting with mild hypochromic microcytic anaemia and splenomegaly since 2(1/2) 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/beta-thalassaemia disease. To provide proper genetic counselling for this family, a definitive diagnosis of beta-thalassaemia was achieved using molecular analysis. We identified a rare initiation codon mutation (ATG-->AGG) of the beta-globin gene in combination with the Hb E mutation (codon 26: GAG-->AAG). 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 beta-globin expression and was considered as beta(0)-thalassaemia, the relatively mild phenotype in our patients may be attributed to a strong association between this mutation and the -158 (G)gamma (C-->T) polymorphism, an XmnI cleavage site (+), resulting in a high propensity of postnatal gamma-globin expression and ameliorating the clinical phenotypes.
Viprakasit
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V
Department of Paediatrics-Siriraj Thalassaemia Research Programme and WHO Collaborating Centre for the Control of Haemoglobinopathies, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand. sivvp@mahidol.ac.th
Chinchang
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W
Suwanthol
L
L
Tanphaichitr
V S
VS
D000747:Anemia, Hypochromic / Q000235:genetics; D044466:Asian People / Q000235:genetics; D002648:Child; D018387:Codon, Initiator / Q000235:genetics*; D005192:Family Health; D005914:Globins / Q000235:genetics*; D006239:Haplotypes; D006446:Hemoglobin E / Q000235:genetics; D006801:Humans; D008297:Male; D005810:Multigene Family / Q000235:genetics; D010375:Pedigree; D017354:Point Mutation; D013785:Thailand; D017086:beta-Thalassemia / Q000175:diagnosis
D018387:Codon, Initiator; D005914:Globins; D006446:Hemoglobin E