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R411C mutation of the ALAS2 gene encodes a pyridoxine‐responsive enzyme with low activity
Author(s) -
Furuyama Kazumichi,
Uno Ritsuko,
Urabe Akio,
Hayashi Norio,
Fujita Hiroyoshi,
Kondo Masao,
Sassa Shigeru,
Yamamoto Masayuki
Publication year - 1998
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.1998.01050.x
Subject(s) - missense mutation , pyridoxine , mutant , enzyme , mutation , microbiology and biotechnology , pyridoxine deficiency , gene , enzyme assay , sideroblastic anemia , mutant protein , biology , biochemistry , chemistry
A R411C missense mutation of the erythroid‐specific δ‐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.