Restless legs syndrome: confirmation of linkage to chromosome 12q, genetic heterogeneity, and evidence of complexity.
BACKGROUND
Genes are involved in the etiology of restless legs syndrome, a common sensorimotor disorder.


OBJECTIVE
To replicate and to further characterize our previously reported chromosome 12q linkage results.


METHODS
Family linkage study.


METHODS
A total of 276 individuals from 19 families have been examined using a selection of markers spanning the identified candidate interval on chromosome 12q.


RESULTS
Two-point analyses of individual pedigrees indicated that 5 kindreds were consistent with linkage to chromosome 12q. When considering these 5 pedigrees along with the family in which linkage was originally reported, we observed a maximum 2-point logarithm-of-odds score of 5.67 (at theta = 0.10; for marker D12S1636; autosomal recessive) and a maximum multipoint logarithm-of-odds score of 8.84 between the interval defined by markers D12S326 and D12S304. Furthermore, our results also suggest the presence of heterogeneity in restless legs syndrome as linkage was formally excluded across the region in 6 pedigrees. Interestingly, significantly higher periodic leg movements during sleep indices were observed for all probands with restless legs syndrome from linked families.


CONCLUSIONS
These results support the presence of a major restless legs syndrome-susceptibility locus on chromosome 12q, which has been designated as RLS1, and also suggest that at least one additional locus may be involved in the origin of this prevalent condition.
Desautels
Alex
A
Centre d'étude du sommeil, Hôpital du Sacré-Coeur de Montréal, Canada.
Turecki
Gustavo
G
Montplaisir
Jacques
J
Xiong
Lan
L
Walters
Arthur S
AS
Ehrenberg
Bruce L
BL
Brisebois
Kateri
K
Desautels
Amelie K
AK
Gingras
Yves
Y
Johnson
William G
WG
Lugaresi
Elio
E
Coccagna
Giorgio
G
Picchietti
Daniel L
DL
Lazzarini
Alice
A
Rouleau
Guy A
GA
D002874:Chromosome Mapping; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D008040:Genetic Linkage / Q000235:genetics*; D005819:Genetic Markers / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D006801:Humans; D008126:Lod Score; D008297:Male; D010375:Pedigree; D012148:Restless Legs Syndrome / Q000235:genetics* / Q000503:physiopathology; D012893:Sleep Wake Disorders / Q000235:genetics / Q000503:physiopathology
D005819:Genetic Markers