Glycyl tRNA synthetase mutations in Charcot-Marie-Tooth disease type 2D and distal spinal muscular atrophy type V.
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.
Antonellis
Anthony
A
Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Ellsworth
Rachel E
RE
Sambuughin
Nyamkhishig
N
Puls
Imke
I
Abel
Annette
A
Lee-Lin
Shih-Queen
SQ
Jordanova
Albena
A
Kremensky
Ivo
I
Christodoulou
Kyproula
K
Middleton
Lefkos T
LT
Sivakumar
Kumaraswamy
K
Ionasescu
Victor
V
Funalot
Benoit
B
Vance
Jeffery M
JM
Goldfarb
Lev G
LG
Fischbeck
Kenneth H
KH
Green
Eric D
ED
D000595:Amino Acid Sequence; D002607:Charcot-Marie-Tooth Disease / Q000145:classification / Q000235:genetics*; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D005799:Genes, Dominant; D006032:Glycine-tRNA Ligase / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009134:Muscular Atrophy, Spinal / Q000145:classification / Q000235:genetics*; D020125:Mutation, Missense; D010375:Pedigree; D020161:Physical Chromosome Mapping; D017386:Sequence Homology, Amino Acid
D006032:Glycine-tRNA Ligase