MEDNIK Syndrome found in Quebec families sharing a common ancestor
Canadian researchers have discovered the MEDNIK Syndrome, an incapacitating genetic condition, according to the latest edition of PLoS Genetics. Dr. Patrick Cossette, a professor Université de Montréal and scientist at the Université de Montréal Hospital Research Centre (CRCHUM), led a group of researchers who found the MEDNIK Syndrome is caused by a new mutation in the AP1S1 gene.
MEDNIK syndrome was discovered in a group of families from the Kamouraska region of Quebec who share a common ancestor. Caused by a mutation in the AP1S1 gene, the syndrome is characterized by mental retardation, enteropathy, deafness, and peripheral neuropathy, ichthyosis, and keratodermia (i.e. MEDNIK).
''Our observations strongly suggest that MEDNIK Syndrome is caused by impaired development of various neural networks, including the spinal chord, the inner ear and possibly the brain (retardation),” notes Dr. Cossette.
''Disruption of the AP1S1 gene in humans may be associated with more widespread perturbation in the development of various organs, including the gut and the skin. These results suggest interesting avenues for both basic and clinical research to improve our understanding of the mechanisms underlying MEDNIK and related genetic neurocutaneous syndromes.”
The study was conducted in collaboration with researchers from the Ontario Institute for Cancer Research, McGill University, the Université de Sherbrooke and the Centre hospitalier régional du Grand-Portage in Rivière-du-Loup.
Using zebrafish as an animal model, they team observed that loss of the AP1S1 gene resulted in broad defects, including severe motor deficits due to impairment of spinal cord development.
After inducing zebrafish with the human AP1S1 gene, instead of their native gene, the researchers discovered that the normal human type could rescue these developmental deficits but not the AP1S1 gene bearing the disease-related mutation. This research appears to be the first report of a mutation in human AP1S1.
About AP1S1 gene in MEDNIK
The AP1S1 gene encodes for a small subunit of an adaptor protein complex (AP-1) involved in the organisation and transport of many other proteins within the cell. Interference with these pathways could result in perturbation of cellular organisation and be detrimental for the development of specific cell subpopulations, as observed respectively in the skin and the spinal cord.
Partners in research:
This study was funded by the Canadian Genetic Disease Network, the Canadian Institutes of Health Research, the Fonds de la recherche en santé du Québec, Genome Canada and Genome Quebec.
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To read the study
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Source :
Communications Department, CHUM
Media contact:
Nathalie Forgue
Communications advisor, CHUM
Telephone: 514-890-8000, Ext. 14342
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