Determination of the breakpoint and molecular diagnosis of a common α‐thalassaemia‐1 deletion in the Indian population

The previously described South African type α‐thalassaemia‐1 mutation was identified in Indian HbH patients using a polymerase chain reaction (PCR) strategy. A multiplex PCR assay was devised to detect heterozygotes and homozygotes. This α‐thalassaemia‐1 mutation was found to be the commonest determinant causing HbH disease in this population. In one family this mutation was found in combination with a novel splice donor mutation α2 IVS I‐1 (G→A). Characterization of the breakpoint junction sequence revealed, in addition to a 23 kb deletion, that there was an addition of ∼160 bp bridging the breakpoints. Similar to other deletions in the α‐globin gene cluster, there is an Alu repeat‐mediated mechanism for the origin of the deletion.