MEDNIK syndrome is a rare genetic disease with autosomal recessive transmission, several cases of which have been identified in four families in the Kamouraska region of Quebec. Characterized by several severe abnormalities in the intestine, skin and ear (which gave it its name: Mental retardation, Enteropathy, Deafness, Neuropathy, Ichthyosis, Keratodermia), this disease leads to death before adolescence. MEDNIK syndrome is caused by a mutation in the AP1S1 gene, located on chromosome 7 and encoding the σ1A subunit of the Adaptor protein-1 complex (AP-1). Patients in the 4 Kamouraska families have the same splice site mutation that results in the exclusion of exon 3 and the introduction of a premature stop codon in exon 4, thus generating a truncated σ1A protein with only 19 aa (rather than 158). Although a zebrafish model exists, we believe that the generation of a mammalian model would allow a more detailed understanding of the pathogenic mechanism of MEDNIK syndrome. Such a model would indeed make it possible to study the function of AP-1 in a physiological context closer to humans, and possibly to test therapeutic approaches.

Principal investigator: Pr Stéphane Lefrancois (INRS)
Collaborator: Pr Nicolas Pilon (UQAM)
Laureate: 2019 Collaborative Research Grant