title: Whole exome sequencing reveals mutations in NARS2 and PARS2, encoding the mitochondrial asparaginyl-tRNA synthetase and prolyl-tRNA synthetase, in patients with Alpers syndrome.
abstract: Alpers syndrome is a progressive neurodegenerative disorder that presents in infancy or early childhood and is characterized by diffuse degeneration of cerebral gray matter. While mutations in POLG1, the gene encoding the gamma subunit of the mitochondrial DNA polymerase, have been associated with Alpers syndrome with liver failure (Alpers-Huttenlocher syndrome), the genetic cause of Alpers syndrome in most patients remains unidentified. With whole exome sequencing we have identified mutations in NARS2 and PARS2, the genes encoding the mitochondrial asparaginyl-and prolyl-tRNA synthetases, in two patients with Alpers syndrome. One of the patients was homozygous for a missense mutation (c.641C>T, p.P214L) in NARS2. The affected residue is predicted to be located in the stem of a loop that participates in dimer interaction. The other patient was compound heterozygous for a one base insertion (c.1130dupC, p.K378 fs*1) that creates a premature stop codon and a missense mutation (c.836C>T, p.S279L) located in a conserved motif of unknown function in PARS2. This report links for the first time mutations in these genes to human disease in general and to Alpers syndrome in particular.
authors: Department of Pediatrics, University of Gothenburg, The Queen Silvia's Children Hospital Gothenburg, Sweden.
authors: Kalliopi
authors: K
authors: Sofou
authors: Department of Clinical Chemistry, University of Gothenburg, Sahlgrenska University Hospital Gothenburg, Sweden.
authors: Gittan
authors: G
authors: Kollberg
authors: Department of Clinical Chemistry, University of Gothenburg, Sahlgrenska University Hospital Gothenburg, Sweden.
authors: Maria
authors: M
authors: Holmström
authors: Bioinformatics Core Facility, University of Gothenburg Gothenburg, Sweden.
authors: Marcela
authors: M
authors: Dávila
authors: Department of Pediatrics, University of Gothenburg, The Queen Silvia's Children Hospital Gothenburg, Sweden.
authors: Niklas
authors: N
authors: Darin
authors: Department of Medical Biochemistry and Cell Biology, University of Gothenburg Gothenburg, Sweden.
authors: Claes M
authors: CM
authors: Gustafsson
authors: Department of Clinical Chemistry, University of Gothenburg, Sahlgrenska University Hospital Gothenburg, Sweden.
authors: Elisabeth
authors: E
authors: Holme
authors: Department of Pathology, University of Gothenburg, Sahlgrenska University Hospital Gothenburg, Sweden.
authors: Anders
authors: A
authors: Oldfors
authors: Department of Pediatrics, University of Gothenburg, The Queen Silvia's Children Hospital Gothenburg, Sweden.
authors: Már
authors: M
authors: Tulinius
authors: Department of Clinical Chemistry, University of Gothenburg, Sahlgrenska University Hospital Gothenburg, Sweden.
authors: Jorge
authors: J
authors: Asin-Cayuela
keywords: Alpers syndrome; NARS2; PARS2; whole exome sequencing
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