Absent phenotypic expression of X-linked sideroblastic anemia in one of 2 brothers with a novel ALAS2 mutation

Mario Cazzola, Alison May, Gaetano Bergamaschi, Paola Cerani, Sara Ferrillo, David F. Bishop

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)4236-4238
Number of pages3
JournalBlood
Volume100
Issue number12
DOIs
Publication statusPublished - Dec 1 2002

ASJC Scopus subject areas

  • Hematology

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