Determination of the breakpoint and molecular diagnosis of a common alpha-thalassaemia-1 deletion in the Indian population.

The previously described South African type alpha-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 alpha-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 alpha2 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 approximately 160 bp bridging the breakpoints. Similar to other deletions in the alpha-globin gene cluster, there is an Alu repeat-mediated mechanism for the origin of the deletion.