Suggestive evidence for linkage for restless legs syndrome on chromosome 19p13.
Five loci for restless legs syndrome (RLS) on chromosomes 12q, 14q, 9p, 2q, and 20p (RLS1-RLS5) have been mapped in RLS families, with a recessive in the first and autosomal-dominant mode of inheritance in the latter cases. Investigations of further RLS families showed evidence for genetic locus heterogeneity. We have conducted a genome-wide linkage analysis in a large RLS family of Italian origin with 12 affected members in 3 generations using 5,861 single nucleotide polymorphisms (SNP, 6K Illumina). Linkage analysis was performed under an autosomal-dominant model with a complete penetrance, an allele frequency of 0.003 and a phenocopy rate of 0.005. The genome-wide scan resulted in suggestive evidence for linkage on chromosome 19p with maximum multipoint logarithm of the odds score of 2.61 between markers rs754292 and rs273265. The locus was replicated in a family-based association study in a set of 159 trios of European origin. This study provides evidence for a further RLS locus, thus supporting the picture of RLS as a genetically heterogenous complex trait.
Kemlink
David
D
Institute of Human Genetics, GSF-National Research Center for Environment and Health, Neuherberg-Munich, Germany.
Plazzi
Giuseppe
G
Vetrugno
Roberto
R
Provini
Federica
F
Polo
Olli
O
Stiasny-Kolster
Karin
K
Oertel
Wolfgang
W
Nevsimalova
Sona
S
Sonka
Karel
K
Högl
Birgit
B
Frauscher
Birgit
B
Hadjigeorgiou
Georgios M
GM
Pramstaller
Peter P
PP
Lichtner
Peter
P
Meitinger
Thomas
T
Müller-Myshok
Bertram
B
Winkelmann
Juliane
J
Montagna
Pasquale
P
D000328:Adult; D000368:Aged; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics*; D004247:DNA / Q000235:genetics; D005260:Female; D005799:Genes, Dominant; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007558:Italy; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D012148:Restless Legs Syndrome / Q000235:genetics*
D004247:DNA