title: Deleterious mutation in the mitochondrial arginyl-transfer RNA synthetase gene is associated with pontocerebellar hypoplasia.
abstract: Homozygosity mapping was performed in a consanguineous Sephardic Jewish family with three patients who presented with severe infantile encephalopathy associated with pontocerebellar hypoplasia and multiple mitochondrial respiratory-chain defects. This resulted in the identification of an intronic mutation in RARS2, the gene encoding mitochondrial arginine-transfer RNA (tRNA) synthetase. The mutation was associated with the production of an abnormally short RARS2 transcript and a marked reduction of the mitochondrial tRNA(Arg) transcript in the patients' fibroblasts. We speculate that missplicing mutations in mitochondrial aminoacyl-tRNA synthethase genes preferentially affect the brain because of a tissue-specific vulnerability of the splicing machinery.
authors.affiliation: Pediatric Neurology Unit, Hadassah-Hebrew University Medical Center, Jerusalem, 91120, Israel.
authors.forename: Simon
authors.initials: S
authors.lastname: Edvardson
authors.forename: Avraham
authors.initials: A
authors.lastname: Shaag
authors.forename: Olga
authors.initials: O
authors.lastname: Kolesnikova
authors.forename: John Moshe
authors.initials: JM
authors.lastname: Gomori
authors.forename: Ivan
authors.initials: I
authors.lastname: Tarassov
authors.forename: Tom
authors.initials: T
authors.lastname: Einbinder
authors.forename: Ann
authors.initials: A
authors.lastname: Saada
authors.forename: Orly
authors.initials: O
authors.lastname: Elpeleg
mesh_terms: D001126:Arginine-tRNA Ligase / Q000235:genetics*; D001483:Base Sequence; D002531:Cerebellum / Q000002:abnormalities* / Q000201:enzymology*; D002675:Child, Preschool; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D003241:Consanguinity; D018076:DNA, Complementary / Q000235:genetics; D004272:DNA, Mitochondrial / Q000235:genetics; D005260:Female; D050259:Genes, Mitochondrial; D006239:Haplotypes; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007585:Jews / Q000235:genetics; D008279:Magnetic Resonance Imaging; D008297:Male; D008928:Mitochondria / Q000201:enzymology; D009154:Mutation; D010375:Pedigree; D011149:Pons / Q000002:abnormalities* / Q000201:enzymology*
chemical_list: D018076:DNA, Complementary; D004272:DNA, Mitochondrial; D001126:Arginine-tRNA Ligase