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

Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, WA 98104, USA.
The American Journal of Human Genetics (Impact Factor: 10.99). 06/2009; 84(5):692-7. DOI: 10.1016/j.ajhg.2009.04.008
Source: PubMed

ABSTRACT 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.

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Available from: Wendy H Raskind, Apr 26, 2014
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    • "to numbers of growth factors such as epidermal growth factor and nerve growth factor in vitro [9]. Although IFRD1 modulates the pathophysiology of human cystic fibrosis lung disease through regulation of the neutrophil effector function [10], IFRD1 is a candidate gene for autosomal-dominant sensory/motor neuropathy with ataxia, which is a rare neurological disorder whose phenotype involves both the central and peripheral nervous systems in humans [11]. Accordingly, TIS7 has been implicated in the regulation of cell growth and differentiation, in addition to the pathogenesis of various diseases, through modulating patterns of gene expression. "
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