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Autosomal dominant restless legs syndrome maps to chromosome 20p13 (RLS‐5) in a Dutch kindred
Author(s) -
Sas Antonetta M.G.,
Di Fonzo Alessio,
Bakker Stef L.M.,
Simons Erik J.,
Oostra Ben A.,
MaatKievit Anneke J.,
Boon Agnita J.W.,
Bonifati Vincenzo
Publication year - 2010
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.23248
Subject(s) - locus (genetics) , genetics , restless legs syndrome , haplotype , genetic linkage , lod score , snp , pedigree chart , biology , gene mapping , chromosome , gene , single nucleotide polymorphism , genotype , neuroscience , neurology
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. © 2010 Movement Disorder Society