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Molecular defects of erythroid 5-aminolevulinate synthase in X-linked sideroblastic anemia

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Abstract

The erythroid-specific isozyme of 5-aminolevulinate synthase (ALAS2), the first and ratelimiting enzyme of heme biosynthesis, is expressed concomitantly with the differentiation and maturation of the erythroid cell in order to accommodate generation of the large amounts of heme required for hemoglobin production. During the past few years the ALAS2 gene and its transcript have been characterized and the amino acid sequence of the enzyme deduced. The human genetic disorder X-linked sideroblastic anemia, previously postulated to be caused by defects of ALAS, has now been analyzed at the molecular and tissue-specific level. A heterogeneous group of point mutations in the catalytic domain of the ALAS2 enzyme has been found to cause the disorder. Impaired activity of recombinant mutant ALAS2 enzymes has also been demonstrated. Characterization of molecular defects in individuals with X-linked sideroblastic anemia has provided improved diagnosis for at-risk family members.

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Author notes

  1. Timothy C. Cox

    Present address: Telethon Institute of Genetics and Medicine, San Raffaele International Biomedical Science Park, 20132, Milano, Italy

Authors and Affiliations

  1. Department of Medicine, University of Oklahoma College of Medicine and Veterans Administration Medical Center, 73104, Oklahoma City, Oklahoma

    Sylvia S. Bottomley

  2. Department of Biochemistry, University of Adelaide, 5005, Adelaide, South Australia

    Brian K. May & Timothy C. Cox

  3. Department of Human Genetics, Mount Sinai School of Medicine, 10029, New York, New York

    Philip D. Cotter & David F. Bishop

Authors
  1. Sylvia S. Bottomley
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  2. Brian K. May
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  3. Timothy C. Cox
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  4. Philip D. Cotter
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  5. David F. Bishop
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Bottomley, S.S., May, B.K., Cox, T.C. et al. Molecular defects of erythroid 5-aminolevulinate synthase in X-linked sideroblastic anemia. J Bioenerg Biomembr 27, 161–168 (1995). https://doi.org/10.1007/BF02110031

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  • DOI: https://doi.org/10.1007/BF02110031

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