R411C mutation of the ALAS2 gene encodes a pyridoxine-responsive enzyme with low activity.
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.
Furuyama
K
K
Department of Biochemistry, Tohoku University School of Medicine, Sendai, Japan.
Uno
R
R
Urabe
A
A
Hayashi
N
N
Fujita
H
H
Kondo
M
M
Sassa
S
S
Yamamoto
M
M
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
D000624:5-Aminolevulinate Synthetase; D011736:Pyridoxine