Glycyl tRNA synthetase mutations in Charcot-Marie-Tooth disease type 2D and distal spinal muscular atrophy type V.

Abstract

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.

• Authors: Anthony Antonellis, Rachel E Ellsworth, Nyamkhishig Sambuughin, Imke Puls, Annette Abel, Shih-Queen Lee-Lin, Albena Jordanova, Ivo Kremensky, Kyproula Christodoulou, Lefkos T Middleton, Kumaraswamy Sivakumar, Victor Ionasescu, Benoit Funalot, Jeffery M Vance, Lev G Goldfarb, Kenneth H Fischbeck, Eric D Green
• Journal: American journal of human genetics (Am J Hum Genet) Vol. 72 Issue 5 Pg. 1293-9 (May 2003) ISSN: 0002-9297 [Print] United States
• PMID: 12690580 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Glycine-tRNA Ligase

Topics

• Amino Acid Sequence
• Charcot-Marie-Tooth Disease (classification, genetics)
• Chromosomes, Human, Pair 7 (genetics)
• DNA Mutational Analysis
• Female
• Genes, Dominant
• Glycine-tRNA Ligase (genetics)
• Humans
• Male
• Molecular Sequence Data
• Muscular Atrophy, Spinal (classification, genetics)
• Mutation, Missense
• Pedigree
• Physical Chromosome Mapping
• Sequence Homology, Amino Acid