Variant screening of the coding regions of MEIS1 in patients with restless legs syndrome

Abstract

Restless legs syndrome (RLS) is a common and genetically complex neurologic disease presenting with an urge to move the legs and dysesthesias in the evening and at times of rest. Genome-wide association studies have linked single nucleotide polymorphisms in MEIS1 and 3 other loci to an increased susceptibility to RLS.1,–,3 However, to date, only one potentially causal variant has been reported.4 Therefore, we screened the coding regions and exon-intron boundaries of MEIS1 for variants, which by exerting a strong phenotypic effect could provide a basis for assessing the function of the gene in RLS. ### Methods. Using Idaho LightScanner high-resolution melting curve analysis, we screened DNA of 188 patients with RLS of a first discovery sample (72.8% female, mean age 60.0 ± 11.2 years), all harboring RLS risk alleles of MEIS1 (G/T or G/G for rs2300478), for aberrant melting patterns (e-Methods on the Neurology ® Web site at www.neurology.org). Exons showing changes suggestive of variants were sequenced on an ABI Prism 3730 sequencer, and variants identified were subsequently genotyped in an independent German sample (henceforth termed “second sample”) consisting of 735 patients with RLS (70.8% female, mean age 61.5 ± 14.2 years) and 735 unrelated control subjects (74.5% female, mean age 59.8 ± 11.3 years) by matrix-assisted laser desorption ionization/time-of-flight mass spectrometry. Disease segregation was evaluated in one family with the p.R272H mutation of …