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Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
A Novel ALAS2 Mutation Resulting in Variable Phenotypes and Pyridoxine Response in a Family with X-linked
Jee-Soo Lee1,2, JaYoon Gu1,3, Hyun Ju Yoo1,3
1Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea.
Abstract:
We report a novel ALAS2 gene mutation c.1315A>G (p.Lys439Glu) identified in a family, which caused evidently different hematologic phenotypes. The proband was a 17-year-old man with severe microcytic hypochromic anemia, excessive ring sideroblasts in the bone marrow, and iron overload. A hemizygous ALAS2 mutation in exon 9, c.1315A>G (p.Lys439Glu), was identified through sequence analysis. We assume that this amino acid substitution affects the enzymatic activity of ALAS2 by affecting its interaction with the cofactor pyridoxal 5'-phosphate, since the patient was responsive to pyridoxine treatment. This novel mutation likely accounts for variable hematologic phenotypes in the family of this patient: his 15-year-old hemizygous brother was asymptomatic, while his heterozygous mother was mildly anemic.
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