Autosomal dominant restless legs syndrome maps to chromosome 20p13 (RLS-5) in a Dutch kindred
Six chromosomal loci have been mapped for restless legs syndrome (RLS) through family-based linkage analysis (RLS-1 to RLS-6), but confirmation has met with limited success, and causative mutations have not yet been identified. We ascertained a large multigenerational Dutch family with RLS of early onset (average 18 years-old). The clinical study included a follow-up of 2 years. To map the underlying genetic defect, we performed a genome-wide scan for linkage using high-density SNP microarrays. A single, strong linkage peak was detected on chromosome 20p13, under an autosomal-dominant model, in the region of the RLS-5 locus (maximum multipoint LOD score 3.02). Haplotype analysis refined the RLS-5 critical region from 5.2 to 4.5 megabases. In conclusion, we provide the first confirmation of the RLS-5 locus, and we reduce its critical region. The identification of the underlying mutation might reveal an important susceptibility gene for this common movement disorder.
|Keywords||Genetics, Linkage mapping, RLS, RLS-5, Restless legs syndrome, adolescent, adult, article, autosomal dominant disorder, child, chromosome 20p, clinical article, female, follow up, gene locus, gene mapping, gene mutation, genetic analysis, genetic linkage, haplotype, human, male, preschool child, priority journal, restless legs syndrome, school child, single nucleotide polymorphism|
|Persistent URL||dx.doi.org/10.1002/mds.23248, hdl.handle.net/1765/21013|
Sas, A.M.G., Di Fonzo, A., Bakker, S.L.M., Simons, E.J., Oostra, B.A., Maat-Kievit, A.A., … Bonifati, V.. (2010). Autosomal dominant restless legs syndrome maps to chromosome 20p13 (RLS-5) in a Dutch kindred. Movement Disorders, 25(11), 1715–1722. doi:10.1002/mds.23248