title: 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.
authors.affiliation: Xenon Genetics Research, Xenon Genetics Inc., Burnaby, British Columbia V5G 4W8, Canada.
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Lafreniere
authors.forename: Marcia L E
authors.initials: ML
authors.lastname: MacDonald
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Dube
authors.forename: Julie
authors.initials: J
authors.lastname: MacFarlane
authors.forename: Mary
authors.initials: M
authors.lastname: O'Driscoll
authors.forename: Bernard
authors.initials: B
authors.lastname: Brais
authors.forename: Sebastien
authors.initials: S
authors.lastname: Meilleur
authors.forename: Ryan R
authors.initials: RR
authors.lastname: Brinkman
authors.forename: Owen
authors.initials: O
authors.lastname: Dadivas
authors.forename: Terry
authors.initials: T
authors.lastname: Pape
authors.forename: Christele
authors.initials: C
authors.lastname: Platon
authors.forename: Chris
authors.initials: C
authors.lastname: Radomski
authors.forename: Jenni
authors.initials: J
authors.lastname: Risler
authors.forename: Jay
authors.initials: J
authors.lastname: Thompson
authors.forename: Ana-Maria
authors.initials: AM
authors.lastname: Guerra-Escobio
authors.forename: Gudarz
authors.initials: G
authors.lastname: Davar
authors.forename: Xandra O
authors.initials: XO
authors.lastname: Breakefield
authors.forename: Simon N
authors.initials: SN
authors.lastname: Pimstone
authors.forename: Roger
authors.initials: R
authors.lastname: Green
authors.forename: William
authors.initials: W
authors.lastname: Pryse-Phillips
authors.forename: Y Paul
authors.initials: YP
authors.lastname: Goldberg
authors.forename: H Banfield
authors.initials: HB
authors.lastname: Younghusband
authors.forename: Michael R
authors.initials: MR
authors.lastname: Hayden
authors.forename: Robin
authors.initials: R
authors.lastname: Sherrington
authors.forename: Guy A
authors.initials: GA
authors.lastname: Rouleau
authors.forename: Mark E
authors.initials: ME
authors.lastname: Samuels
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002874:Chromosome Mapping; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D003241:Consanguinity; D005190:Family; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D009477:Hereditary Sensory and Autonomic Neuropathies / Q000235:genetics*; D006801:Humans; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009523:Newfoundland and Labrador; D016366:Open Reading Frames; D010375:Pedigree; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid
chemical_list: D005819:Genetic Markers; D009419:Nerve Tissue Proteins