IFRD1 is a candidate gene for SMNA on chromosome 7q22-q23.
We have established strong linkage evidence that supports mapping autosomal-dominant sensory/motor neuropathy with ataxia (SMNA) to chromosome 7q22-q32. SMNA is a rare neurological disorder whose phenotype encompasses both the central and the peripheral nervous system. In order to identify a gene responsible for SMNA, we have undertaken a comprehensive genomic evaluation of the region of linkage, including evaluation for repeat expansion and small deletions or duplications, capillary sequencing of candidate genes, and massively parallel sequencing of all coding exons. We excluded repeat expansion and small deletions or duplications as causative, and through microarray-based hybrid capture and massively parallel short-read sequencing, we identified a nonsynonymous variant in the human interferon-related developmental regulator gene 1 (IFRD1) as a disease-causing candidate. Sequence conservation, animal models, and protein structure evaluation support the involvement of IFRD1 in SMNA. Mutation analysis of IFRD1 in additional patients with similar phenotypes is needed for demonstration of causality and further evaluation of its importance in neurological diseases.
Brkanac
Zoran
Z
Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, WA 98104, USA. zbrkanac@u.washington.edu
Spencer
David
D
Shendure
Jay
J
Robertson
Peggy D
PD
Matsushita
Mark
M
Vu
Tiffany
T
Bird
Thomas D
TD
Olson
Maynard V
MV
Raskind
Wendy H
WH
D001259:Ataxia / Q000235:genetics*; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D015417:Hereditary Sensory and Motor Neuropathy / Q000235:genetics*; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics*; D009154:Mutation; D010375:Pedigree
C490045:IFRD1 protein, human; D017874:Immediate-Early Proteins