Restless legs syndrome (RLS) is a sensorimotor disorder that often starts at a young age and has a chronic progression throughout life. It has a very high incidence, affecting 10% of the general population. The majority of cases are familial and the genetic nature of the disorder has been demonstrated in twin studies. RLS segregates in an autosomal dominant way in the majority of families. This data has incited a search for genetic factors responsible for RLS using linkage as the approach. Dr. Rouleau's laboratory has one of the world's largest collections of RLS pedigrees. These families are mostly of French Canadian (FC) origin. / Using these families, two novel candidate loci, on chromosomes 16p and 20p, were discovered. Also, previously described candidate loci on chromosomes 9p and 14q were replicated in this cohort of families. / A duplication of a large part of a functional candidate gene in the locus on chromosome 20, Signal Regulatory Protein beta 1 (SIRPB1), was discovered in individuals affected with RLS from a FC pedigree, in which linkage to this locus was described. The duplication segregates with the disease status in the family, but its role in RLS pathogenesis has yet to be demonstrated. / No disease-causing mutations were discovered in the chromosome 16 locus. Analysis of several functional and positional candidate genes in previously described loci on chromosomes 12 and 14 did not reveal disease-causing mutations. / A follow up of these studies is necessary in order to confirm the implication of SIRPB1 in RLS pathogenesis, and to detect novel gene(s) whose deregulation leads to this disorder.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.115893 |
| Date | January 2008 |
| Creators | Levchenko, Anastasia. |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Department of Human Genetics.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 002826869, proquestno: AAINR66681, Theses scanned by UMI/ProQuest. |
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