Mitochondrial myopathy and sideroblastic anemia
-Rare developmental defect during embryogenesis
-Rare genetic disease
-Rare hematologic disease
-Rare neurologic disease
Comment:
The p.Ser435Gly (c.1303A>G) mutation is located at the ribosomal protein S4-like domain of the gene, while other reported YARS2 mutations are all within the catalytic domain e.g. (p.Phe52Leu). The proband with p.Ser435Gly mutation showed more severe symptoms and an earlier onset than previously reported patients (PMID:24430573).
Riley et al. (2010) reported 2 sibs, born of consanguineous Lebanese parents, with MLASA2. Both developed transfusion-dependent sideroblastic anemia in infancy, followed by progressive lethargy, muscle weakness, and exercise intolerance in childhood associated with persistent lactic acidemia. The ... Riley et al. (2010) reported 2 sibs, born of consanguineous Lebanese parents, with MLASA2. Both developed transfusion-dependent sideroblastic anemia in infancy, followed by progressive lethargy, muscle weakness, and exercise intolerance in childhood associated with persistent lactic acidemia. The proband was reported to be wheelchair-dependent by age 17 years, and developed respiratory insufficiency necessitating ventilation. Both also had dysphagia requiring enteral nutrition in their teens. The proband had hypertrophic cardiomyopathy, which was not noted in his affected sister. Cognitive function remained normal in both patients. Skeletal muscle biopsy of the proband showed subsarcolemmal mitochondrial aggregates, some ragged-red fibers, and decreased cytochrome oxidase staining. Another Lebanese patient from an unrelated consanguineous family had a similar disorder, with the addition of delayed motor milestones and later onset of anemia at age 7 years. Despite the lack of blood transfusions, she was able to walk and showed only a mild skeletal myopathy and mild muscle weakness at age 24 years.
By genomewide linkage analysis followed by candidate gene sequencing of 2 consanguineous Lebanese families with MLASA2, Riley et al. (2010) identified a homozygous mutation in the YARS2 gene (F52L; 610957.0001). In vitro functional expression assays showed that the ... By genomewide linkage analysis followed by candidate gene sequencing of 2 consanguineous Lebanese families with MLASA2, Riley et al. (2010) identified a homozygous mutation in the YARS2 gene (F52L; 610957.0001). In vitro functional expression assays showed that the mutant YARS2 protein had an overall 9-fold loss of catalytic efficiency. The findings indicated that the mutation resulted in reduced aminoacylation efficiency, causing a defect in mitochondrial protein synthesis with a subsequent impairment of mitochondrial respiratory activity.