A Novel Locus for Autosomal Dominant Restless Legs Syndrome
EB Skehan, MMA Abdulrahim, CK Hand, NA Parfrey. University College Cork, Cork, Ireland
Background: Restless Legs Syndrome (RLS) is a sleep-related disorder characterised by an irresistible urge to move the lower limbs associated with unpleasant sensations. Symptoms present while at rest, generally in the evening, and are relieved, at least partially and temporarily, by movement. RLS affects 5-10% of the general population, frequently resulting in chronic sleep deprivation. Drugs targeting the dopamine pathway have shown therapeutic benefit. RLS may develop secondary to conditions such as renal failure, iron deficiency and pregnancy. More commonly, RLS is a familial disorder inherited in an autosomal dominant manner. RLS loci have been identified in six distinct genomic regions by linkage analysis. Association mapping has highlighted a further four areas of interest. To date, no causative gene has been identified.
Design: We recruited a three generation Irish family with autosomal dominant RLS. Eighteen members participated in this study of whom 11 are affected. Institutional ethical approval was obtained and all participants gave written informed consent. Symptom questionnaires were completed and neurological examinations were undertaken. Genomic DNA was extracted from venous blood samples. Polymorphic microsatellite markers were amplified by PCR and samples were genotyped using the ABI3130 genetic analyser. LOD scores were generated using FASTLINK software.
Results: Linkage was excluded from all known RLS loci. A genome-wide scan identified a region of linkage with a maximum LOD score of 3.59, at a theta value of 0. Recombination events, identified by haplotype analysis, define a genetic region which corresponds to 2.5 Mb. This disease gene containing region has approximately 100 known genes. A number of candidate genes have been identified based on potential involvement in RLS pathogenesis and are the subject of further study.
Conclusions: We have successfully identified a novel locus for autosomal dominant Restless Legs Syndrome. Completion of this stage of the study enables us to attempt to identify the causative gene in this family and, thus, to further the understanding of RLS pathogenesis.
Monday, March 22, 2010 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 225, Monday Morning