Identification of an arginine452 to histidine substitution in the erythroid 5-aminolaevulinate synthetase gene in a large pedigree with X-linked hereditary sideroblastic anaemia

• Published in: European journal of haematology Vol. 58; no. 1; pp. 1 - 4
• Main Authors: Edgar, A. J., Losowsky, M. S., Noble, J. S., Wickramasinghe, S. N.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-01-1997; Blackwell
• Subjects: 5-Aminolevulinate Synthetase - genetics; ALAS2; Amino Acid Sequence; Anemia, Sideroblastic - genetics; Anemias. Hemoglobinopathies; Arginine - genetics; Biological and medical sciences; Diseases of red blood cells; Female; Hematologic and hematopoietic diseases; hereditary sideroblastic anaemia; Histidine - genetics; Humans; Male; Medical sciences; Molecular Sequence Data; mutation; Pedigree; Point Mutation; Sequence Analysis; Human; Acyltransferases; Sex linked character; Enzyme; Family study; Transferases; Hemopathy; Sideroblastic anemia; 5-Aminolevulinate synthase; Hereditary; Myelodysplastic syndrome; Genetic disease; Gene; Point mutation; X-Chromosome
• ISSN: 0902-4441; 1600-0609
• DOI: 10.1111/j.1600-0609.1997.tb01402.x

:  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 HhaI restriction enzyme digest site. An HhaI 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.