A novel mutation of the erythroid-specific gamma-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 with pyridoxine-responsive sideroblastic anemia. Activity of the mutant delta-aminolevulinate synthase protein expressed in vitro was 15.1% compared with the normal control, but was increased up to 34.5% by the addition of pyridoxal 5'-phosphate, consistent with the clinical response of the patient to pyridoxine treatment. The same mutation was also detected in genomic DNa from the oral mucosal membrane of the patiet; however, it was not detected in other family member. These findings suggest that this G663A mutation is responsible for sideroblastic anemia in the proband, and may be an index mutation in this pedigree.
T10 T11 T12 T13 T1 T2 T3 T4 T5 T6 T7 T8 T9
GENE-N GENE-Y GENE-N GENE-N CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL GENE-Y GENE-Y
G663A erythroid-specific delta-aminolevulinate synthase G663A erythroid-specific gamma-Aminolevulinate synthase pyridoxine delta-aminolevulinate pyridoxal 5'-phosphate pyridoxine delta-aminolevulinate pyridoxine gamma-Aminolevulinate ALAS2 delta-aminolevulinate synthase