Mutations in a neuronal specific isoform of WNK1 cause
this very serious disease
MONTREAL, June 10 /CNW Telbec/ - A major discovery that details the
existence of a neuronal specific form of the WNK1 gene, henceforth referred to
as the WNK1/HSN2 isoform, was recently completed by the research group of
Dr. Guy A. Rouleau and published in the scientific journal The Journal of
Clinical Investigation. The group led by Dr. Rouleau is part of the University
of Montreal Hospital Centre (CHUM), the CHUM Research Centre (CRCHUM) and the
Sainte-Justine University Hospital Centre. Dr. Rouleau is also a professor at
the University of Montreal. Their recent results will hereafter help to
explain all the cases of hereditary neuropathy type II.
Hereditary sensory and autonomic neuropathy type II (HSANII) is a severe
and early onset disorder that starts early during childhood. It is
characterized by loss of perception to pain, touch and heat attributable to a
loss of peripheral sensory nerves in the lower and upper limbs. Unfortunately
no therapy is currently available for individuals suffering from hereditary
neuropathy type II. In 2004, Dr. Rouleau's team identified the DNA sequence of
HSN2 as encoding a novel gene but their more recent investigations have now
shown that this sequence is more precisely linked to the expression of a
WNK1 isoform that is exclusively detected in the nervous system. Till their
discovery, the presence of mutations in WNK1 were only observed in individual
suffering from a rare form of hypertension known as Gordon syndrome and no
WNK1 isoform were exclusively expressed in the nervous system. The observation
of mutations specific to the WNK1/HSN2 isoform in individuals with hereditary
sensory and autonomic type II will henceforth allow the generation of animal
models of the disease and help to better understand the implication of this
gene and its mutations in the sensorial loss mentioned above.
Despite the severity of the symptoms observed in hereditary sensory and
autonomic neuropathy type II, this important discovery points to the role of
proteins like WNK1/HSN2 that are involved in the perception of pain and
henceforth open new avenues for the development of pain treatments. A better
understanding of the disease also provide a valuable genetic test to asses the
risk or the cause of the disease in individuals at risk or presenting symptoms
This study of WNK1/HSN2 was realized in the laboratory of Dr. Rouleau by
two postdoctoral fellows, Dr. Nathalie Girard and Dr Masoud Shekarabi.
Dr. Laurence Faivre from the Hôpital d'enfants, CHU Dijon, also participated
to this study.
This work was funded by the Canadian Institutes of Health Research.
The article is available online at: www.jci.org/articles/view/34088/pdf.
About the CHUM : www.chumtl.qc.ca
About the CHUM Research Centre : www.chumtl.qc.ca/research-centre.fr.html
About University of Montreal : www.umontreal.ca
For further information:
For further information: Nathalie Forgue, Communications Advisor, Centre
hospitalier de l'Université de Montréal, (514) 890-8000, poste 14342, Pager:
(514) 801-5762; Sylvain-Jacques Desjardins, International Press Attaché,
Université de Montréal, (514) 343-7583