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X‐linked sideroblastic anaemia due to a mutation in the erythroid 5‐aminolaevulinate synthase gene leading to an arginine 170 to leucine substitution
Author(s) -
Edgar A. J.,
Vidyatilake H. M. S.,
Wickramasinghe S. N.
Publication year - 1998
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.1600-0609.1998.tb01061.x
Subject(s) - missense mutation , transversion , biology , exon , microbiology and biotechnology , sideroblastic anemia , genetics , mutation , leucine , arginine , gene , 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, a G561T transversion in exon 5 of the gene. Previously, the mutation G561A has been shown to be responsible for sideroblastic anaemia in females and thought to be lethal in males (1). The mutation G561T results in the loss of an Msp A1‐I cutting site. Analysis of Msp A1‐I restriction enzyme digests of amplified exon 5 genomic DNA from other family members revealed that the proband's mother, aunt and youngest sister, who were not anaemic, were heterozygous carriers of the mutation. The G561T mutation results in an arginine to leucine substitution at amino acid residue 170. This arginine residue is conserved in both the erythroid and housekeeping ALAS in vertebrates as well as in all other known ALAS proteins and is located in a predicted alpha‐helix region close to the amino‐terminus of the enzymatic region of the protein.