A novel mutation of the erythroid-specific delta-aminolaevulinate synthasegene in a patient with X-linked sideroblastic anaemia

A novel missense mutation, A1754G, in exon 11 of the erythroid-specific del ta-aminolaevulinate synthase gene (ALAS2) was identified in a Japanese male with sideroblastic anaemia. ALAS activity in bone marrow cells of the pati ent was reduced to 53.3 % of the normal control. Consistent with this findi ng, activity of a bacterially expressed ALAS2 mutant protein harbouring thi s mutation was 19.5% compared with the normal control, but was increased up to 31.6% by the addition of pyridoxal 5'-phosphate (PLP) in vitro. RFLP an alysis with Bsp HI restriction revealed that his mother was a carrier of th e mutation. These findings suggest that A1754G mutation was inherited in th is family in a manner consistent with X-linked inheritance, and is responsi ble for sideroblastic anaemia in the patient.