Published November 14, 2002
| Version v1
Journal article
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Absent phenotypic expression of X-linked sideroblastic anemia in one of 2 brothers with a novel ALAS2 mutation
Authors/Creators
- 1. From the Department of Hematology and the Department of Internal Medicine and Medical Therapy, University of Pavia Medical School, and Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico S. Matteo, Pavia, Italy; the Department of Haematology, University of Wales College of Medicine, Cardiff, Wales; and the Department of Human Genetics, Mount Sinai School of Medicine, New York, NY.
Description
X-linked sideroblastic anemia (XLSA) is caused by mutations in the erythroid-specific 5-aminolevulinic acid synthase (ALAS2)gene. Hemizygous males have microcytic anemia and iron overload. A 38-year-old male presented with this phenotype (hemoglobin [Hb] 7.6 g/dL, mean corpuscular volume [MCV] 64 fL, serum ferritin 859 μg/L), and molecular analysis of ALAS2 showed a mutation 1731G>A predicting an Arg560His amino acid change. A 36-year-old brother was hemizygous for this mutation and expressed the mutated ALAS2 mRNA in his reticulocytes, but showed almost no phenotypic expression. All 5 heterozygous females from this family, including the 3 daughters of the nonanemic hemizygous male, showed marginally increased red-cell distribution width (RDW). Although variable penetrance for XLSA in males has been previously described, this is the first report showing that phenotypic expression can be absent in hemizygous males. This observation is relevant to genetic counseling, emphasizing the importance of gene-based diagnosis.