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

Am J Hum Genet. 2004 May;74(5):1064-73. doi: 10.1086/420795.

Ronald G Lafreniere ¹, Marcia L E MacDonald, Marie-Pierre Dube, Julie MacFarlane, Mary O'Driscoll, Bernard Brais, Sebastien Meilleur, Ryan R Brinkman, Owen Dadivas, Terry Pape, Christele Platon, Chris Radomski, Jenni Risler, Jay Thompson, Ana-Maria Guerra-Escobio, Gudarz Davar, Xandra O Breakefield, Simon N Pimstone, Roger Green, William Pryse-Phillips, Y Paul Goldberg, H Banfield Younghusband, Michael R Hayden, Robin Sherrington, Guy A Rouleau, Mark E Samuels

Affiliations

Affiliation

1 Xenon Genetics Research, Xenon Genetics Inc., Burnaby, British Columbia V5G 4W8, Canada.

PMID: 15060842 DOI: 10.1086/420795

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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