Hb Iraq-Halabja ?10 (A7) Ala?Val (GCC?GTC): A new ?-chain silent variant in a family with multiple Hb disorders
✍ Scribed by Deutsch, S.; Darbellay, R.; Offord, R.; Frutiger, A.; Kister, J.; Wajcman, H.; Beris, Ph.
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 356 KB
- Volume
- 61
- Category
- Article
- ISSN
- 0361-8609
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✦ Synopsis
A patient originating from Iraq was referred to our laboratory upon suspicion of a hemoglobinopathy. Routine hematological tests revealed a microcytic and slightly anemic phenotype with an elevated HbA 2 suggestive of -thalassemia. Samples were obtained for several members of the family which upon examination revealed highly heterogeneous phenotypes that prompted us to investigate the case further. Sequencing of the -globin gene and ␣ cluster mapping in the propositus and his brother showed a previously undescribed -globin variant:Hb Iraq-Halabja, 10(A7) Ala→Val (GCC→GTC), associated with  0 -thalassemia IVS-2 nt1 G→A and either ␣-thal-2-3.7 kb deletion (brother), or ␣-globin gene triplication anti-3.7 kb type (propositus). Detailed functional studies of the variant gave a normal oxygenation curve, a normal heterotopic action of 2,3 DPG, and normal heat stability and isopropanol precipitation tests. The variant shows a clear difference in migration properties compared to normal -chain only when run on PAGE urea Triton. As expected, ␣/-globin mRNA ratios were influenced by the concomitant presence of an ␣-globin gene pathology and the  0 thalassemia and not by the presence of the -globin variant which apparently is clinically silent. Am.