A novel mutation of the erythroid-specific delta-aminolevulinate synthase gene in a patient with non-inherited pyridoxine-responsive sideroblastic anemia

A novel missense mutation, G663A, In exon 5 of the erythroid-specific delta -aminolevulinate synthase gene (ALAS2) was identified in a Japanese male wi th pyridoxine-responsive sideroblastic anemia. Activity of the mutant delta -aminolevulinate synthase protein expressed in vitro was 15.1% compared wit h the normal control, but was increased up to 34.5% by the addition of pyri doxal 5'-phosphate, consistent with the clinical response of the patient to pyridoxine treatment, The same mutation was also detected in genomic DNA f rom the oral mucosal membrane of the patient; however, it was not detected in other family members. These findings suggest that this G663A mutation is responsible for sideroblastic anemia in the proband, and may be an index m utation in this pedigree, Am. J. Hematol. 62:112-114, 1999. (C) 1999 Wiley- Liss, Inc.