Étude des facteurs génétiques dans la pathophysiologie du somnambulisme
Sleepwalking is a common sleep disorder and it belongs to the family of NREM parasomnias. Despite decades of research, its pathophysiology remains poorly understood. Family and twin studies show that a strong hereditary component is involved. However, very few molecular studies have been conducted to identify the genes involved and there is still no consensus on the mode of transmission in families. This Master’s thesis contains two separate studies which will attempt to address these two problems. The aim of the first study was to determine whether genetic variants in the Adenosine Deaminase (ADA) gene were enriched in the sleepwalking population compared to healthy sleepers. The entire gene was sequenced in 251 sleepwalking patients from Montreal and Montpellier as well as in 94 control subjects with no personal or family history of sleepwalking. No genetic variants were enriched in sleepwalking patients compared to healthy sleepers and public genetic databases. In the second study, the first objective was to determine the mode of transmission of sleepwalking in 20 French-Canadian families. The second objective was to measure the recurrence risk as well as the relative risk for siblings and children of index patients. In our cohort, sleepwalking was transmitted mainly in an autosomal dominant mode with reduced penetrance. The recurrence risks for first-degree relatives were: lifetime 0.48 to 0.56, in childhood 0.43 to 0.56, and in adulthood 0.14 to 0.35. The relative risks for first-degree relatives were: lifetime 6.96 to 8.12, in childhood 1.48 to 4.06 and in adulthood 4.67 to 11.67 higher than the general population. Further molecular studies, such as exome sequencing, and genetic linkage studies in families will be needed in order to identify new candidate genes that can act as biomarkers. This would allow the development of an independent test for the diagnosis and ultimately have implications for targeted therapeutic approaches.
Pedigrees Sleepwalking NREM parasomnia Adenosine deaminase Genetics Sequencing