title: Two novel mutations of GARS in Korean families with distal hereditary motor neuropathy type V.
abstract: Glycyl-tRNA synthetase (GARS), which encodes the enzyme responsible for charging tRNA(Gly) with glycine in both the cytoplasm and mitochondria, is implicated to Charcot-Marie-Tooth disease 2D (CMT2D) and distal hereditary motor neuropathy type V (dHMN-V). We performed whole exome sequencing (WES) to identify the genetic defects in the two dHMN families. WES revealed several decades of non-synonymous variants in the CMT and aminoacyl-tRNA synthetase genes. The subsequent capillary sequencing for family members and controls revealed two novel causative mutations, c.598G>A (D200N) and c.794C>T (S265F), in the GARS gene in each dHMN family. Both mutations were cosegregated with affected individuals in each family, and were not found in the 200 controls. The mutation sites were well conserved between the different species and in silico analysis predicted that both mutations may affect protein function. Therefore, we believe that these two novel GARS mutations are the underlying causes of the dHMN phenotype.
authors.affiliation: Department of Biological Science, Kongju National University, Gongju, South Korea.
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Lee
authors.forename: Jin
authors.initials: J
authors.lastname: Park
authors.forename: Khriezanou
authors.initials: K
authors.lastname: Nakhro
authors.forename: Jin Mo
authors.initials: JM
authors.lastname: Park
authors.forename: Yoon-Mi
authors.initials: YM
authors.lastname: Hur
authors.forename: Byung-Ok
authors.initials: BO
authors.lastname: Choi
authors.forename: Ki Wha
authors.initials: KW
authors.lastname: Chung
mesh_terms: D000328:Adult; D017668:Age of Onset; D020968:Brachial Plexus Neuritis / Q000150:complications; D002607:Charcot-Marie-Tooth Disease / Q000145:classification / Q000235:genetics; D004568:Electrodiagnosis; D005260:Female; D020233:Gait Disorders, Neurologic / Q000209:etiology / Q000235:genetics; D006032:Glycine-tRNA Ligase / Q000235:genetics*; D009477:Hereditary Sensory and Autonomic Neuropathies / Q000235:genetics*; D006801:Humans; D007723:Korea; D008875:Middle Aged; D009154:Mutation / Q000235:genetics / Q000502:physiology; D010375:Pedigree; D055815:Young Adult
chemical_list: D006032:Glycine-tRNA Ligase