Identification of a novel gene (HSN2) causing hereditary sensory and autonomic neuropathy type II through the Study of Canadian Genetic Isolates.

Abstract

Hereditary sensory and autonomic neuropathy (HSAN) type II is an autosomal recessive disorder characterized by impairment of pain, temperature, and touch sensation owing to reduction or absence of peripheral sensory neurons. We identified two large pedigrees segregating the disorder in an isolated population living in Newfoundland and performed a 5-cM genome scan. Linkage analysis identified a locus mapping to 12p13.33 with a maximum LOD score of 8.4. Haplotype sharing defined a candidate interval of 1.06 Mb containing all or part of seven annotated genes, sequencing of which failed to detect causative mutations. Comparative genomics revealed a conserved ORF corresponding to a novel gene in which we found three different truncating mutations among five families including patients from rural Quebec and Nova Scotia. This gene, termed "HSN2," consists of a single exon located within intron 8 of the PRKWNK1 gene and is transcribed from the same strand. The HSN2 protein may play a role in the development and/or maintenance of peripheral sensory neurons or their supporting Schwann cells.

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@article{Lafrenire2004IdentificationOA, title={Identification of a novel gene (HSN2) causing hereditary sensory and autonomic neuropathy type II through the Study of Canadian Genetic Isolates.}, author={Ronald G. Lafreni{\`e}re and Marcia L E Macdonald and Marie-Pierre Dub{\'e} and Julie Macfarlane and Mary C O'Driscoll and Bernard Brais and S{\'e}bastien Meilleur and Ryan R. Brinkman and Owen Dadivas and Terry D Pape and Christ{\`e}le Platon and Chris C Radomski and Jenni K Risler and Jay Thompson and Ana-Maria Guerra-Escobio and Gudarz Davar and Xandra O Breakefield and Simon Neil Pimstone and R. C. Green and William E M Pryse-Phillips and Yigal Paul Goldberg and H. B. Younghusband and Michael R. Hayden and Robin P. Sherrington and Guy Rouleau and Mark E. Samuels}, journal={American journal of human genetics}, year={2004}, volume={74 5}, pages={1064-73} }