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

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.