Tania Cruz Marino1, Hélène Villeneuve2, Josianne Leblanc3, Caroline Duranceau2, Philippe Caron2, Charles Morin4, Marcel Milot4, Raphaëlle Chrétien4, Maude-Marie Gagnon5, Jean Mathieu6, Benjamin Ellezam7, Daniela Buhas8. 1. Department of Laboratory Medicine, CIUSSS Saguenay-Lac-St-Jean, Saguenay, QC, Canada. tania.cruzmarino.csssc@ssss.gouv.qc.ca. 2. Department of Endocrinology, CIUSSS Saguenay-Lac-St-Jean, Saguenay, QC, Canada. 3. Department of Laboratory Medicine, CIUSSS Saguenay-Lac-St-Jean, Saguenay, QC, Canada. 4. Department of Pediatrics, CIUSSS Saguenay-Lac-St-Jean, Saguenay, QC, Canada. 5. Clinique des Maladies Neuromusculaires, CIUSSS Saguenay-Lac-St-Jean, Saguenay, QC, Canada. 6. Department of Neurology, Université de Sherbrooke, QC, Sherbrooke, Canada. 7. Department of Pathology, CHU Sainte-Justine, Université de Montréal, Montreal, QC, Canada. 8. Division of Medical Genetics, Department of Specialized Medicine; Department of Human Genetics, McGill University, Montreal, QC, Canada.
Abstract
PURPOSE: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is more prevalent in some founder populations, but relatively unexplored in Canada. This study aimed at investigating the French-Canadian patients through phenotypic and genotypic characterization. METHOD: Phenotype and demographic characterization were done for 12 affected individuals belonging to eight unrelated families. Samples from 11 cases were analyzed in a molecular clinical laboratory, and muscle biopsies were reviewed for two individuals with a limb-girdle muscle dystrophy. RESULTS: The clinical phenotype was similar to that observed in European Caucasian populations but differed in the non-endocrine spectrum from the American-reported series of cases. Two cases exhibited a limb-girdle muscle dystrophy, and we found preliminary evidence of a mitochondrial dysfunction, since all three biopsies examined showed COX-deficient fibers in excess of what would be expected for age. Electron microscopy showed mitochondrial accumulation without abnormal cristea or inclusions. The c.1616C > T variant in the AIRE gene was responsible for 100% of APECED cases in the French-Canadian population of Saguenay-Lac-Saint-Jean in Quebec, Canada. CONCLUSIONS: We report the first series of French-Canadian cases affected with APECED. The Saguenay-Lac-Saint-Jean region was uncovered as a new founder population for this condition. Muscle biopsy findings expanded the range of previously described APECED-related myopathology. Long term follow-up of our genetically homogeneous French-Canadian cases may help determine if the c.1616C > T variant increases the risk of muscle involvement. A neonatal screening program is under consideration to prevent undesired life-threatening endocrine manifestations.
PURPOSE: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is more prevalent in some founder populations, but relatively unexplored in Canada. This study aimed at investigating the French-Canadian patients through phenotypic and genotypic characterization. METHOD: Phenotype and demographic characterization were done for 12 affected individuals belonging to eight unrelated families. Samples from 11 cases were analyzed in a molecular clinical laboratory, and muscle biopsies were reviewed for two individuals with a limb-girdle muscle dystrophy. RESULTS: The clinical phenotype was similar to that observed in European Caucasian populations but differed in the non-endocrine spectrum from the American-reported series of cases. Two cases exhibited a limb-girdle muscle dystrophy, and we found preliminary evidence of a mitochondrial dysfunction, since all three biopsies examined showed COX-deficient fibers in excess of what would be expected for age. Electron microscopy showed mitochondrial accumulation without abnormal cristea or inclusions. The c.1616C > T variant in the AIRE gene was responsible for 100% of APECED cases in the French-Canadian population of Saguenay-Lac-Saint-Jean in Quebec, Canada. CONCLUSIONS: We report the first series of French-Canadian cases affected with APECED. The Saguenay-Lac-Saint-Jean region was uncovered as a new founder population for this condition. Muscle biopsy findings expanded the range of previously described APECED-related myopathology. Long term follow-up of our genetically homogeneous French-Canadian cases may help determine if the c.1616C > T variant increases the risk of muscle involvement. A neonatal screening program is under consideration to prevent undesired life-threatening endocrine manifestations.
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