Compound heterozygous mutations in glycyl-tRNA synthetase are a proposed cause of systemic mitochondrial disease

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dc.contributor.authorMcMillan, Hugh J
dc.contributor.authorSchwartzentruber, Jeremy
dc.contributor.authorSmith, Amanda
dc.contributor.authorLee, Suzie
dc.contributor.authorChakraborty, Pranesh
dc.contributor.authorBulman, Dennis E
dc.contributor.authorBeaulieu, Chandree L
dc.contributor.authorMajewski, Jacek
dc.contributor.authorBoycott, Kym M
dc.contributor.authorGeraghty, Michael T
dc.date.accessioned2015-12-18T10:55:11Z
dc.date.available2015-12-18T10:55:11Z
dc.date.issued2014-03-26
dc.identifier.citationBMC Medical Genetics. 2014 Mar 26;15(1):36
dc.identifier.urihttp://dx.doi.org/10.1186/1471-2350-15-36
dc.identifier.urihttp://hdl.handle.net/10393/33708
dc.description.abstractAbstract Background Glycyl-tRNA synthetase (GARS) is an aminoacyl-tRNA synthetase (ARS) that links the amino acid glycine to its corresponding tRNA prior to protein translation and is one of three bifunctional ARS that are active within both the cytoplasm and mitochondria. Dominant mutations in GARS cause rare forms of Charcot-Marie-Tooth disease and distal spinal muscular atrophy. Case presentation We report a 12-year old girl who presented with clinical and biochemical features of a systemic mitochondrial disease including exercise-induced myalgia, non-compaction cardiomyopathy, persistent elevation of blood lactate and alanine and MRI evidence of mild periventricular leukomalacia. Using exome sequencing she was found to harbor compound heterozygous mutations within the glycyl-tRNA synthetase (GARS) gene; c.1904C > T; p.Ser635Leu and c.1787G > A; p.Arg596Gln. Each mutation occurred at a highly conserved site within the anticodon binding domain. Conclusion Our findings suggest that recessive mutations in GARS may cause systemic mitochondrial disease. This phenotype is distinct from patients with previously reported dominant mutations in this gene, thereby expanding the spectrum of disease associated with GARS dysregulation.
dc.titleCompound heterozygous mutations in glycyl-tRNA synthetase are a proposed cause of systemic mitochondrial disease
dc.typeJournal Article
dc.date.updated2015-12-18T10:55:11Z
dc.language.rfc3066en
dc.rights.holderMcMillan et al.; licensee BioMed Central Ltd.
CollectionLibre accès - Publications // Open Access - Publications

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