Édith Breton1,2, Cécilia Légaré1,2, Gayle Overend3, Simon-Pierre Guay1,4, Darren Monckton3, Jean Mathieu2,5, Cynthia Gagnon2,5, Louis Richer2,6, Benjamin Gallais2,5,7, Luigi Bouchard1,2,8. 1. Department of Biochemistry & Functional Genomics, Université de Sherbrooke, Sherbrooke, Québec J1E 4K8, Canada. 2. Groupe de recherche interdisciplinaire sur les maladies neuromusculaires (GRIMN), Centre intégré universitaire de santé et de services sociaux (CIUSSS) du Saguenay-Lac-St-Jean - Hôpital de Jonquière, Saguenay, Québec G7X 7X2, Canada. 3. Institute of Molecular, Cell & Systems Biology, University of Glasgow, Glasgow G12 8QQ, United Kingdom. 4. Department of Specialized Medicine, Division of Medical Genetics, McGill University Health Centre, Montreal, QC H4A 3J1, Canada. 5. Centre de recherche Charles-Le-Moyne-Saguenay-Lac-Saint-Jean sur les innovations en santé (CR-CSIS), Université de Sherbrooke, Saguenay, Québec G7H 5H6, Canada. 6. Department of Health Sciences, Université du Québec à Chicoutimi (UQAC), Saguenay, Québec G7H 2B1, Canada. 7. ÉCOBES - Recherche et transfert, Cégep de Jonquière, Saguenay, Québec G7X 7W2, Canada. 8. Department of Medical Biology, Centre intégré universitaire de santé et de services sociaux (CIUSSS) du Saguenay-Lac-St-Jean - Hôpital de Chicoutimi, Saguenay, Québec G7H 5H6, Canada.
Abstract
Aim: Myotonic dystrophy type 1 (DM1) is caused by an unstable trinucleotide (CTG) expansion at the DMPK gene locus. Cognitive dysfunctions are often observed in the condition. We investigated the association between DMPK blood DNA methylation (DNAm) and cognitive functions in DM1, considering expansion length and variant repeats (VRs). Method: Data were obtained from 115 adult-onset DM1 patients. Molecular analyses consisted of pyrosequencing, small pool PCR and Southern blot hybridization. Cognitive functions were assessed by validated neuropsychological tests. Results: For patients without VRs (n = 103), blood DNAm at baseline independently contributed to predict cognitive functions 9 years later. Patients with VRs (n = 12) had different DNAm and cognitive profiles. Conclusion: DNAm allows to better understand DM1-related cognitive dysfunction etiology.
Aim: Myotonic dystrophy type 1 (DM1) is caused by an unstable trinucleotide (CTG) expansion at the DMPK gene locus. Cognitive dysfunctions are often observed in the condition. We investigated the association between DMPK blood DNA methylation (DNAm) and cognitive functions in DM1, considering expansion length and variant repeats (VRs). Method: Data were obtained from 115 adult-onset DM1patients. Molecular analyses consisted of pyrosequencing, small pool PCR and Southern blot hybridization. Cognitive functions were assessed by validated neuropsychological tests. Results: For patients without VRs (n = 103), blood DNAm at baseline independently contributed to predict cognitive functions 9 years later. Patients with VRs (n = 12) had different DNAm and cognitive profiles. Conclusion: DNAm allows to better understand DM1-related cognitive dysfunction etiology.
Entities:
Keywords:
copy number variant; epigenetics; genetics; neuromuscular disease; neuropsychology