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A strong genetic contribution to the etiology of restless legs syndrome (RLS, OMIM 102300) was suggested by the first descriptions of its symptoms.1 More than half of patients report other affected family members and extended RLS families have since been recruited. However, neurologists and geneticists seeking to identify causally related variants have realized that RLS genetics is challenging. Genome-wide linkage analyses of RLS families have met with limited success. These analyses either failed altogether or resulted in only borderline significant lod scores. The finding that the highest lod scores achieved were below the simulated scores in the respective families provided indirect evidence for the complexity of RLS. To date, five RLS loci (RLS1-5, on chromosomes 12q, 14q, 9p, 2q, and 20p) identified through linkage studies in …
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