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Identification of an arginine 452 to histidine substitution in the erythroid 5‐aminolaevulinate synthetase gene in a large pedigree with X‐linked hereditary sideroblastic anaemia
Author(s) -
Edgar A. J.,
Losowsky M. S.,
Noble J. S.,
Wickramasinghe S. N.
Publication year - 1997
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/j.1600-0609.1997.tb01402.x
Subject(s) - biology , exon , single strand conformation polymorphism , genetics , point mutation , microbiology and biotechnology , gene , locus (genetics) , complementary dna , transition (genetics) , coding region , histidine , arginine , cytosine , mutation , amino acid
The coding region of the erythroid 5‐aminolaevulinate synthetase gene (ALAS2) from a large pedigree with pyridoxine‐responsive X‐linked hereditary sideroblastic anaemia was examined for mutations. In three affected males from this pedigree, single strand conformational polymorphism (SSCP) analysis showed anomalous migration of a PCR product spanning exon 9. Sequencing of amplified genomic DNA from one of these affected males revealed a guanine to adenine transition at nucleotide 1407 of the cDNA sequence in exon 9 of the gene. This mutation results in the loss of an Hha I restriction enzyme digest site. An Hha I digest assay demonstrated the presence of this mutation in other affected males but not in unaffected males and unrelated individuals. The point mutation results in an arginine to histidine substitution at amino acid residue 452. The arginine residue is conserved in both the erythroid and housekeeping ALAS genes in all known vertebrate sequences. This arginine is located in the middle of a predicted alpha‐helix.