Hb A2 Episkopi – a novel δ-globin chain variant [HBD:c.428C>T] in a family of mixed Cypriot–Lebanese descent

Carsten W. Lederer, Eleni Pavlou, George A. Tanteles, Paola Evangelidou, Carolina Sismani, Annita Kolnagou, Maria Sitarou, Soteroulla Christou, Michael Hadjigavriel, Marina Kleanthous
2016 Hematology  
Marina Kleanthous (2016) : Hb A 2 Episkopi -a novel δ-globin chain variant [HBD:c.428C>T] in a family of mixed Cypriot-Lebanese descent, Hematology, ABSTRACT Objectives: Thalassaemia is a potentially lethal inherited anaemia, caused by reduced or absent synthesis of globin chains. Measurement of the minor adult haemoglobin Hb A 2 , combining αwith δ-globin, is critical for the routine diagnosis of carrier status for αor β-thalassaemia. Here, we aim to characterize a novel δ-globin variant, Hb A
more » ... 2 Episkopi, in a single family of mixed Lebanese and Cypriot ancestry with mild hypochromic anaemia and otherwise normal globin genotype, which also presents with a coincidental 0.78-Mb sequence duplication on chromosome 1 (1q44) and developmental abnormalities. Methods: Analyses included comprehensive haematological analyses, cation-exchange highperformance liquid chromatography (CE-HPLC), cellulose acetate electrophoresis (CAE), Sanger sequencing and structure-based stability predictions for Hb A 2 Episkopi. Results: The GCT > GTT missense mutation, underlying Hb A 2 Episkopi, HBD:c.428C > T, introduces a cd142 codon change in the mature protein, resulting in reduced normal Hb A 2 amounts and a novel, less abundant Hb A 2 variant (HGVS: HBD:p.A143V), detectable as a delayed peak by CE-HPLC. The latter was in line with structure-based stability predictions, which indicated that the substitution of a marginal, non-helical and non-interface residue, five amino acids from the δ-globin chain carboxy-terminus, was moderately destabilizing. Discussion: Detection of the new variant depends on the diagnostic set-up and had failed by CAE and on an independent CE-HPLC system, which, in unfavourable circumstances, may lead to misdiagnoses of β-thalassaemia as α-thalassaemia. Given the mixed background of the affected family, the ethnic origin of the mutation is unclear, and this study thus suggests awareness for possible detection of Hb A 2 Episkopi in both the Cypriot and the Lebanese populations.
doi:10.1080/10245332.2016.1265043 pmid:28007020 fatcat:uny2275lfndnjharorg2njzzx4