Summary. The previously described South African type a-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 a-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 a2 IVS I-1 (G fi 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 a-globin gene cluster, there is an Alu repeat-mediated mechanism for the origin of the deletion. Keywords: a-thalassaemia, PCR, India, AluThe a-thalassaemias are genetic defects characterized by the decrease or complete suppression of synthesis of the a-globin polypeptide chains of haemoglobin. They are the most common single-gene diseases in the world. The a-globin genes are duplicated (a1 and a2) and located within the a gene cluster f2)wf1)wa2)wa1)a2)a1)h1 on the distal short arm region of chromosome 16 (Higgs et al, 1989). This cluster contains four genes and three pseudogenes. Deletions of one ()a) or both () ) )) of these cis-linked genes are the most common causes of the a-thalassaemias. Around 25 different two-gene cis deletions () )) and eight single-gene deletions ()a)