IFRD1 is a candidate gene for SMNA on chromosome 7q22-q23

Am J Hum Genet. 2009 May;84(5):692-7. doi: 10.1016/j.ajhg.2009.04.008. Epub 2009 Apr 30.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Ataxia / genetics*
  • Chromosomes, Human, Pair 7 / genetics*
  • Genetic Predisposition to Disease*
  • Hereditary Sensory and Motor Neuropathy / genetics*
  • Humans
  • Immediate-Early Proteins / genetics*
  • Mutation
  • Pedigree


  • IFRD1 protein, human
  • Immediate-Early Proteins