Glycyl tRNA Synthetase Mutations in Charcot-Marie-Tooth Disease Type 2D and Distal Spinal Muscular Atrophy Type V

• Published in: American journal of human genetics Vol. 72; no. 5; pp. 1293 - 1299
• Main Authors: Antonellis, Anthony, Ellsworth, Rachel E., Sambuughin, Nyamkhishig, Puls, Imke, Abel, Annette, Lee-Lin, Shih-Queen, Jordanova, Albena, Kremensky, Ivo, Christodoulou, Kyproula, Middleton, Lefkos T., Sivakumar, Kumaraswamy, Ionasescu, Victor, Funalot, Benoit, Vance, Jeffery M., Goldfarb, Lev G., Fischbeck, Kenneth H., Green, Eric D.
• Format: Journal Article
• Language: English
• Published: Chicago, IL Elsevier Inc 01-05-2003; University of Chicago Press; The American Society of Human Genetics
• Subjects: Amino Acid Sequence; Biological and medical sciences; Charcot-Marie-Tooth Disease - classification; Charcot-Marie-Tooth Disease - genetics; Chromosomes, Human, Pair 7 - genetics; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; DNA Mutational Analysis; Female; Genes, Dominant; Glycine-tRNA Ligase - genetics; Humans; Male; Medical sciences; Molecular Sequence Data; Muscular Atrophy, Spinal - classification; Muscular Atrophy, Spinal - genetics; Mutation, Missense; Neurology; Pedigree; Physical Chromosome Mapping; Sequence Homology, Amino Acid; Human; Neuromuscular diseases; Nervous system diseases; Enzyme; Pathogenesis; Spinal amyotrophy; Clinical form; Genetic determinism; Genetic disease; Glycine-tRNA ligase; EC 6.1.1.14; Ligases; Charcot Marie Tooth disease; Distal; Central nervous system disease; Degenerative disease; Mutation; Carbon-oxygen ligases; Spinal cord disease
• ISSN: 0002-9297; 1537-6605
• DOI: 10.1086/375039

Charcot-Marie-Tooth disease type 2D (CMT2D) and distal spinal muscular atrophy type V (dSMA-V) are axonal peripheral neuropathies inherited in an autosomal dominant fashion. Our previous genetic and physical mapping efforts localized the responsible gene(s) to a well-defined region on human chromosome 7p. Here, we report the identification of four disease-associated missense mutations in the glycyl tRNA synthetase gene in families with CMT2D and dSMA-V. This is the first example of an aminoacyl tRNA synthetase being implicated in a human genetic disease, which makes genes that encode these enzymes relevant candidates for other inherited neuropathies and motor neuron diseases.