Hb Iraq-Halabja beta 10 (A7) Ala -> Val (GCC -> GTC): A new beta-chain silent variant in a family with multiple Hb disorders

A patient originating from Iraq was referred to our laboratory upon suspici on of a hemoglobinopathy, Routine hematological tests revealed a microcytic and slightly anemic phenotype with an elevated HbA(2) suggestive of beta-t halassemia. Samples were obtained for several members of the family which u pon examination revealed highly heterogeneous phenotypes that prompted us t o investigate the case further. Sequencing of the beta-globin gene and alph a cluster mapping in the propositus and his brother showed a previously und escribed beta-globin variant:Hb Iraq-Halabja, beta 10(A7) Ala-->Val (GCC--> GTC), associated with beta(o)-thalassemia IVS-2 nt1 G-->A and either alpha- thal-2-3.7 kb deletion (brother), or alpha-globin gene triplication anti-3. 7 kb type (propositus), Detailed functional studies of the variant gave a n ormal oxygenation curve, a normal heterotopic action of 2,3 DPG, and normal heat stability and isopropanol precipitation tests, The variant shows a cl ear difference in migration properties compared to normal beta-chain only w hen run on PAGE urea Triton, As expected, alpha/beta-globin mRNA ratios wer e influenced by the concomitant presence of an alpha-globin gene pathology and the beta(o) thalassemia and not by the presence of the beta-globin vari ant which apparently is clinically silent, Am, J, Hematol, 61:187-193, 1999 , (C) 1999 Wiley-Liss, Inc.