Identification of a major susceptibility locus for restless legs syndrome on chromosome 12q

Restless legs syndrome (RLS) is a neurological disorder characterized by le g paresthesia associated with an irresistible urge to move that often inter feres with nocturnal sleep, leading to chronic sleep deprivation. To map ge nes that may play a role in the vulnerability to RLS, a genomewide scan was conducted in a large French-Canadian family. Significant linkage was estab lished on chromosome 12q, for a series of adjacent microsatellite markers w ith a maximum two-point LOD score of 3.42 (recombination fraction .05; P=6 x 10(-4); autosomal recessive mode of inheritance), whereas multipoint link age calculations yielded a LOD score of 3.59. Haplotype analysis refined th e genetic interval, positioning the RLS- predisposing gene in a 14.71-cM re gion between D12S1044 and D12S78. These findings represent the first mappin g of a locus conferring susceptibility to RLS.