RLS3: Fine-mapping of an autosomal dominant locus in a family with intrafamilial heterogeneity

@article{Liebetanz2006RLS3FO,
  title={RLS3: Fine-mapping of an autosomal dominant locus in a family with intrafamilial heterogeneity},
  author={K M Liebetanz and Juliane Winkelmann and Claudia Trenkwalder and Benno P{\"u}tz and Martin Dichgans and Thomas Gasser and Bertram M{\"u}ller-Myhsok},
  journal={Neurology},
  year={2006},
  volume={67},
  pages={320 - 321}
}
A new locus for restless legs syndrome (RLS3) was identified on chromosome 9p24-22. The authors analyzed transmission disequilibrium tests (TDTs) and affecteds-only linkage analysis in one large family of Bavarian origin, taking into account age at onset. P values were 0.0054 for marker D9S1810 for TDT and 0.0009 for the affecteds-only linkage analysis, providing a confirmation of RLS3. This study narrows the region containing the autosomal dominant RLS3 locus to 11.1 cM (16.6 Mbp). 
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43 Citations
Background Citations
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Results Citations
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43 Citations

Autosomal‐dominant locus for restless legs syndrome in French‐Canadians on chromosome 16p12.1

TLDR
An autosomal‐dominant locus for Restless Legs Syndrome (RLS) in a French‐Canadian (FC) pedigree is described and copy number variation and karyotype analyses did not reveal any chromosomal abnormality in the region.

Suggestive evidence for linkage for restless legs syndrome on chromosome 19p13

TLDR
Evidence for a further RLS locus is provided, thus supporting the picture of RLS as a genetically heterogenous complex trait.

Autosomal dominant restless legs syndrome maps to chromosome 20p13 (RLS‐5) in a Dutch kindred

TLDR
The identification of the underlying mutation might reveal an important susceptibility gene for this common movement disorder, and the critical region of the RLS‐5 locus is reduced.

Evidence for linkage of restless legs syndrome to chromosome 9p

TLDR
A family with a rather homogeneous phenotype and very early disease onset represents a unique opportunity to further elucidate the genetic causes of the frequent restless leg syndrome and demonstrates linkage to a locus on chromosome 9p that is probably distinct from RLS3.

Genetics of restless legs syndrome: evidence for a hereditary disorder

TLDR
It appears that familial RLS tends to have an earlier age of onset than sporadic cases, although the clinical characteristics of the two groups are quite similar.

Genetics of restless legs syndrome: evidence for a hereditary disorder

TLDR
It appears that familial RLS tends to have an earlier age of onset than sporadic cases, although the clinical characteristics of the two groups are quite similar.

Genetics of restless legs syndrome

TLDR
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.

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.

[Advances in genetics of restless legs syndrome].

TLDR
The most important findings achieved in genetic studies of RLS are reviewed and it is suggested that it is a highly heritable trait with heritability estimates of about 50%.

Clinical overview and phenomenology of movement disorders

References

SHOWING 1-10 OF 10 REFERENCES

Identification of a major susceptibility locus for restless legs syndrome on chromosome 12q.

TLDR
These findings represent the first mapping of a locus conferring susceptibility to RLS, and positioning the RLS-predisposing gene in a 14.71-cM region between D 12S1044 and D12S78 is refined.

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.

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

TLDR
The segregation pattern found in the authors' families argues for an autosomal allele acting dominantly in RLS families with an early age at onset of symptoms and suggests that RLS is a causative heterogeneous disease.

Descent graphs in pedigree analysis: applications to haplotyping, location scores, and marker-sharing statistics.

TLDR
Algorithms for implementing Thompson's suggestion for codominant markers in the context of automatic haplotyping, estimating location scores, and computing gene-clustering statistics for robust linkage analysis are explored.

Restless legs syndrome: diagnostic criteria, special considerations, and epidemiology. A report from the restless legs syndrome diagnosis and epidemiology workshop at the National Institutes of Health.

Faster sequential genetic linkage computations.

TLDR
A variety of algorithmic improvements are described, which synthesize biological principles with computer science techniques, to effectively restructure the time-consuming computations in genetic linkage analysis.

Genomewide linkage scan identifies a novel susceptibility locus for restless legs syndrome on chromosome 9p.

TLDR
RLS is established as a highly heritable trait, a novel genetic locus for RLS is identified, and the assumption of an autosomal-dominant mode of inheritance is validated, which will facilitate further cloning and identification of the genes.

Pedigree disequilibrium tests for multilocus haplotypes

TLDR
A permutation procedure for the null hypothesis of interest is described, which controls for violation of the assumptions, and a likelihood‐ratio test is proposed, using the expectation‐maximization (E‐M) algorithm to account for haplotype ambiguities.

Autosomal dominant restless legs syndrome maps on chromosome 14q.

TLDR
Significant evidence is shown of linkage to a new locus for RLS on chromosome 14q13-21 region in a 30-member, three-generation Italian family affected by RLS and periodic leg movements in sleep (PLMS), the second RLS locus identified so far and the first consistent with an autosomal dominant inheritance pattern.

SLINK: a general simulation program for linkage analysis

  • Am J Hum Genet 1990;47:A204. Abstract. July
  • 2006