title: Expansion of the QARS deficiency phenotype with report of a family with isolated supratentorial brain abnormalities.
abstract: We describe a family with QARS deficiency due to compound heterozygous QARS mutations, including c.1387G > A (p.R463*) in the catalytic core domain and c.2226C > G (p.Q742H) in the anticodon domain, both previously unreported and predicted damaging. The phenotype of the male index further confirms this specific aminoacyl-transfer RNA (tRNA) synthetase disorder as a novel genetic cause of progressive microcephaly with diffuse cerebral atrophy, severely deficient myelination, intractable seizures, and developmental arrest. However, in contrast to the two hitherto published families, the cerebellum and its myelination are not affected. An awareness that QARS mutations may cause isolated supratentorial changes is crucial for properly directing genetic analysis.
authors.affiliation: Division of Biochemical Diseases, Rm K3-201, Department of Pediatrics, B.C. Children's & Women's Hospital, 4480 Oak Street, Vancouver, BC, V6H 3 V4, Canada.
authors.forename: Ramona
authors.initials: R
authors.lastname: Salvarinova
authors.forename: Cynthia X
authors.initials: CX
authors.lastname: Ye
authors.forename: Andrea
authors.initials: A
authors.lastname: Rossi
authors.forename: Roberta
authors.initials: R
authors.lastname: Biancheri
authors.forename: Elke H
authors.initials: EH
authors.lastname: Roland
authors.forename: Paul
authors.initials: P
authors.lastname: Pavlidis
authors.forename: Colin J
authors.initials: CJ
authors.lastname: Ross
authors.forename: Maja
authors.initials: M
authors.lastname: Tarailo-Graovac
authors.forename: Wyeth W
authors.initials: WW
authors.lastname: Wasserman
authors.forename: Clara D M
authors.initials: CD
authors.lastname: van Karnebeek
mesh_terms: D000604:Amino Acyl-tRNA Synthetases / Q000235:genetics*; D000926:Anticodon; D001921:Brain / Q000002:abnormalities*; D002648:Child; D005190:Family; D020022:Genetic Predisposition to Disease; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008831:Microcephaly / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D010641:Phenotype
chemical_list: D000926:Anticodon; D000604:Amino Acyl-tRNA Synthetases