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Hereditary sideroblastic anaemia due to a mutation in exon 10 of the erythroid 5‐aminolaevulinate synthase gene
Author(s) -
Edgar Aj,
S. N. Wickramasinghe
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.1365-2141.1998.00569.x
Subject(s) - exon , missense mutation , biology , microbiology and biotechnology , genetics , gene , histidine , mutation , complementary dna , point mutation , amino acid
DNA sequencing of the coding region of the erythroid 5‐aminolaevulinate synthase (ALAS2) cDNA from a male with pyridoxine‐responsive sideroblastic anaemia revealed a missense mutation C1622G and a closely linked polymorphism C1612A in exon 10 of the gene. Sequence analysis of the genomic DNA from other family members revealed that the proband's mother and daughter were heterozygous carriers of the mutation, consistent with the X‐linked inheritance. The C1622G mutation results in a histidine to aspartic acid substitution at amino acid residue 524. The histidine residue is conserved in both the erythroid and housekeeping ALAS proteins in vertebrates, all other known ALAS proteins and other oxamine synthases that have pyridoxal 5′‐phosphate as a co‐factor. This histidine is located in a predicted loop, preceding a long alpha‐helix region near the carboxy‐terminus.