Evidence for linkage of restless legs syndrome to chromosome 9p

@article{LohmannHedrich2008EvidenceFL,
  title={Evidence for linkage of restless legs syndrome to chromosome 9p},
  author={Katja Lohmann-Hedrich and Anja Neumann and Andre Kleensang and Thora Lohnau and Hans Muhle and Ana Djarmati and Inke Regina K{\"o}nig and Peter Paul Pramstaller and Eberhard Schwinger and Patricia Kramer and Andreas Ziegler and Ulrich Stephani and Christine Klein},
  journal={Neurology},
  year={2008},
  volume={70},
  pages={686 - 694}
}
Background: Restless legs syndrome (RLS) is a common sensory-motor disorder characterized by paresthesias and an intense urge to move the legs with a considerable familial aggregation. To date, no gene mutation has been found, but five gene loci have been mapped in primary RLS to chromosomes 12q, 14q, 9p, 2q, and 20p (RLS1 through 5). Patients/Methods: We identified a four-generational German RLS family with 37 family members including 15 affected cases. We performed linkage analysis using… 

Figures and Tables from this paper

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

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.

Genetics of restless legs syndrome

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

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 of Restless Legs Syndrome (RLS)

The first functional follow-up studies in the post-GWAS era have implicated expression alterations and forebrain development as well as dysfunctional iron metabolism as the possible downstream effects of the RLS-associated genetic alterations.

Childhood‐onset restless legs syndrome: Clinical and genetic features of 22 families

The positive family history for RLS suggests a genetic cause in most families with at least one additional RLS gene locus, and a trend for an association at two of the three reported susceptibility regions was observed.

Parkin gene modifies the effect of RLS4 on the age at onset of restless legs syndrome (RLS)

  • I. PichlerF. Marroni P. Pramstaller
  • Biology
    American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics
  • 2010
The results suggest that the occurrence of a heterozygous Parkin mutation works in tandem with the gene at the RLS4 locus to lower the AAO in RLS.

Recent advances in the diagnosis, genetics and treatment of restless legs syndrome

An overview on therapeutic options and recent trials is given based on evidence-based management strategies for this common disorder.

References

SHOWING 1-10 OF 38 REFERENCES

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

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.

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

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.

Mode of inheritance and susceptibility locus for restless legs syndrome, on chromosome 12q.

To evaluate the role of the described chromosome 12q locus for restless legs syndrome, two large South Tyrolean families with clinically definite RLS were ascertained and a dominant model and a recessive model for RLS was considered.

Family‐based association study of the restless legs syndrome loci 2 and 3 in a European population

Variable results observed in families of different ethnic groups further corroborate the genetic complexity of RLS and represent the first confirmation of these loci in a mixed European population.

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

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.

A novel autosomal dominant restless legs syndrome locus maps to chromosome 20p13

The authors investigated genetic factors contributing to restless legs syndrome (RLS) by performing a 10-cM genome-wide scan in a large French-Canadian pedigree. They detected an autosomal-dominant

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

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.

Co‐occurrence of restless legs syndrome and Parkin mutations in two families

A large multigenerational family and a smaller family with RLS are presented, and inheritance of RLS was consistent with autosomal dominant transmission, and linkage analysis excluded all three known loci for RLS.

Studies of penetrance and anticipation in five autosomal‐dominant restless legs syndrome pedigrees

In two of the five analyzed pedigrees, there is statistical support for anticipation and variations in penetrance and anticipation suggest possible genetic heterogeneity.

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

A new locus for restless legs syndrome (RLS3) was identified on chromosome 9p24-22 and the region containing the autosomal dominant RLS3 locus is narrowed to 11.1 cM (16.6 Mbp).