title: R411C mutation of the ALAS2 gene encodes a pyridoxine-responsive enzyme with low activity.
abstract: A R411C missense mutation of the erythroid-specific delta-aminolaevulinate synthase (ALAS2) gene was identified in a pedigree with X-linked pyridoxine-responsive sideroblastic anaemia (XLSA). The normal and the mutant cDNAs were expressed in E. coli, and the enzyme protein was purified. ALAS activity of the mutant enzyme was 12% and 25%, when incubated in the absence and the presence of pyridoxal 5'-phosphate, respectively, compared with that of the wild-type enzyme. These findings suggest that the R411C mutation accounts for low ALAS activity and a partial pyridoxine-responsiveness of the disease in the patient.
authors.affiliation: Department of Biochemistry, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Furuyama
authors.forename: R
authors.initials: R
authors.lastname: Uno
authors.forename: A
authors.initials: A
authors.lastname: Urabe
authors.forename: N
authors.initials: N
authors.lastname: Hayashi
authors.forename: H
authors.initials: H
authors.lastname: Fujita
authors.forename: M
authors.initials: M
authors.lastname: Kondo
authors.forename: S
authors.initials: S
authors.lastname: Sassa
authors.forename: M
authors.initials: M
authors.lastname: Yamamoto
mesh_terms: D000624:5-Aminolevulinate Synthetase / Q000235:genetics*; D000293:Adolescent; D000756:Anemia, Sideroblastic / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D011736:Pyridoxine / Q000627:therapeutic use
chemical_list: D000624:5-Aminolevulinate Synthetase; D011736:Pyridoxine