Identification of a novel gene (HSN2) causing hereditary sensory and autonomic neuropathy type II through the Study of Canadian Genetic Isolates.
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.
Lafreniere
Ronald G
RG
Xenon Genetics Research, Xenon Genetics Inc., Burnaby, British Columbia V5G 4W8, Canada.
MacDonald
Marcia L E
ML
Dube
Marie-Pierre
MP
MacFarlane
Julie
J
O'Driscoll
Mary
M
Brais
Bernard
B
Meilleur
Sebastien
S
Brinkman
Ryan R
RR
Dadivas
Owen
O
Pape
Terry
T
Platon
Christele
C
Radomski
Chris
C
Risler
Jenni
J
Thompson
Jay
J
Guerra-Escobio
Ana-Maria
AM
Davar
Gudarz
G
Breakefield
Xandra O
XO
Pimstone
Simon N
SN
Green
Roger
R
Pryse-Phillips
William
W
Goldberg
Y Paul
YP
Younghusband
H Banfield
HB
Hayden
Michael R
MR
Sherrington
Robin
R
Rouleau
Guy A
GA
Samuels
Mark E
ME
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
D005819:Genetic Markers; D009419:Nerve Tissue Proteins