Complex segregation analysis of restless legs syndrome provides evidence for an autosomal dominant mode of inheritance in early age at onset families

@article{Winkelmann2002ComplexSA,
  title={Complex segregation analysis of restless legs syndrome provides evidence for an autosomal dominant mode of inheritance in early age at onset families},
  author={Juliane Winkelmann and Bertram Muller-Myhsok and Hans-Ulrich Wittchen and Bettina Hock and Muriel Prager and Hildegard Pfister and A. Strohle and Ilonka Eisensehr and Martin Dichgans and Thomas Gasser and Claudia Trenkwalder},
  journal={Annals of Neurology},
  year={2002},
  volume={52}
}
A strong familial component of restless legs syndrome (RLS) is known. The objective of this study therefore was to investigate the likely mode of inheritance of RLS. RLS patients and their first‐degree relatives were investigated and classified in RLS affected and RLS nonaffected subjects. Assessments were based on direct, personal standardized diagnostic interviews. Complex segregation analysis was performed with the families stratified according to the mean age at onset of the disease within… 

Segregation Analysis of Restless Legs Syndrome: Possible Evidence for a Major Gene in a Family Study Using Blinded Diagnoses

TLDR
The high rate of phenocopies matches known population frequencies and taken with significant residual familial effects and the lack of evidence for a major gene controlling age of onset, indicates that non-genetic causes of RLS may exist and RLS is a complex disorder.

Two pedigrees with restless legs syndrome in Brazil.

TLDR
The symptoms, the sleep profiles and physiological parameters of two families in which several members present RLS/PLM, a prevalent sleep disorder affecting about 5 to 15% of the population and one that substantially impairs healthy sleep patterns are described.

Analysis of familial and sporadic restless legs syndrome in age of onset, gender, and severity features

TLDR
The analysis supports the prevailing hypothesis that RLS is divided into earlier onset disease with a clear genetic component and later onset disease wich unclear etiology, and that one or more endophenotypes might exist within the disorder which could further characterize these subjects for future genetic studies.

Restless legs syndrome: Epidemiological and clinicogenetic study in a South Tyrolean population isolate

TLDR
The absence of a suggestive linkage signal at the three known RLS susceptibility loci is indicative of further locus heterogeneity of this frequent disorder and encourages further studies to unveil the genetic causes of RLS.

Evidence for further genetic locus heterogeneity and confirmation of RLS‐1 in restless legs syndrome

TLDR
Evidence for linkage on chromosome 12 supports the existence of RLS‐1 and provides evidence for the likelihood of further genetic locus heterogeneity of RLP, and further genome wide linkage analyses have the potential to identify additional RLS loci.

Genetics of restless legs syndrome: An update.

Genetics of restless legs syndrome.

  • J. Winkelmann
  • Biology
    Current neurology and neuroscience reports
  • 2008

Genetics of restless legs syndrome

TLDR
Genome-wide association studies identified variants within intronic or intergenic regions of MEIS1, BTBD9, and MAP2K5/LBOXCOR1 andMEIS1 and LBXCOR1 that have weak and moderate effects and increase the risk of developing RLS.

Genetics in restless legs syndrome.

...

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