title: A novel homozygous YARS2 mutation causes severe myopathy, lactic acidosis, and sideroblastic anemia 2.
abstract: Mitochondrial diseases are associated with defects of adenosine triphosphate production and energy supply to organs as a result of dysfunctions of the mitochondrial respiratory chain. Biallelic mutations in the YARS2 gene encoding mitochondrial tyrosyl-tRNA synthetase cause myopathy, lactic acidosis, and sideroblastic anemia 2 (MLASA2), a type of mitochondrial disease. Here, we report a consanguineous Turkish family with two siblings showing severe metabolic decompensation including recurrent hypoglycemia, lactic acidosis, and transfusion-dependent anemia. Using whole-exome sequencing of the proband and his parents, we identified a novel YARS2 mutation (c.1303A>G, p.Ser435Gly) that was homozygous in the patient and heterozygous in his parents. This mutation is located at the ribosomal protein S4-like domain of the gene, while other reported YARS2 mutations are all within the catalytic domain. Interestingly, the proband showed more severe symptoms and an earlier onset than previously reported patients, suggesting the functional importance of the S4-like domain in tyrosyl-tRNA synthetase.
authors.affiliation: 1] Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan [2] Department of Pediatrics, Tokyo Medical University, Shinjuku, Japan.
authors.forename: Junya
authors.initials: J
authors.lastname: Nakajima
authors.affiliation: Department of Pediatric Metabolism, Ankara University School of Medicine, Ankara, Turkey.
authors.forename: Tuba F
authors.initials: TF
authors.lastname: Eminoglu
authors.affiliation: Department of Pediatrics, Ankara University School of Medicine, Ankara, Turkey.
authors.forename: Goksel
authors.initials: G
authors.lastname: Vatansever
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Mitsuko
authors.initials: M
authors.lastname: Nakashima
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Tsurusaki
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Hirotomo
authors.initials: H
authors.lastname: Saitsu
authors.affiliation: Department of Pediatrics, Tokyo Medical University, Shinjuku, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Kawashima
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Naomichi
authors.initials: N
authors.lastname: Matsumoto
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Miyake
mesh_terms: D000140:Acidosis, Lactic / Q000150:complications / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000756:Anemia, Sideroblastic / Q000150:complications / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D017809:Fatal Outcome; D005260:Female; D006720:Homozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009135:Muscular Diseases / Q000150:complications / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D014448:Tyrosine-tRNA Ligase / Q000235:genetics*; D055815:Young Adult
chemical_list: D014448:Tyrosine-tRNA Ligase