Canadian researchers announce the discovery of MEDNIK, a debilitating genetic syndrome, in a study published December 5 in the open-access journal PLoS Genetics. The team demonstrates that this syndrome is caused by a newly found mutation in the human AP1S1 gene.
Dr. Patrick Cossette and his team discovered MEDNIK syndrome in a group of families in Quebec that share a common ancestor. The syndrome is characterized by mental retardation, enteropathy, deafness, peripheral neuropathy, ichthyosis, and keratodermia (MEDNIK).
The team of researchers observed in a zebrafish model that the loss of the AP1S1 gene results in broad defects, including severe motor deficits due to impairment of spinal cord development. By then inducing the expression of the human AP1S1 gene instead of the zebrafish gene, the research team found that a normal human AP1S1 gene could rescue these developmental deficits, but the AP1S1 gene bearing the disease-related mutation could not.
"Our observations strongly suggest that MEDNIK syndrome is caused by impaired development of various neural networks, including the spinal cord, the inner ear, and possibly the brain," 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 team was composed of researchers from CRCHUM, The Genome Quebec Innovation Centre, McGill University, The Ontario Institute for Cancer Research, Université de Montréal, Ontario Institute for Cancer Research, McGill University, Université de Sherbrooke, and Centre hospitalier régional du Grand-Portage in Rivière-du-Loup.
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CITATION: Montpetit A, Côte´ S, Brustein E, Drouin CA, Lapointe L, et al. (2008) Disruption of AP1S1, Causing a Novel Neurocutaneous Syndrome, Perturbs Development of the Skin and Spinal Cord. PLoS Genet 4(12): e1000296. doi:10.1371/journal.pgen.1000296
A patient's family member will be available for interviews, as well as Dr. Cossette.
Nathalie Forgue, MA
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