Linkage analysis identifies a novel locus for restless legs syndrome on chromosome 2q in a South Tyrolean population isolate.

@article{Pichler2006LinkageAI,
  title={Linkage analysis identifies a novel locus for restless legs syndrome on chromosome 2q in a South Tyrolean population isolate.},
  author={Irene Pichler and Fabio Marroni and Claudia B{\'e}u Volpato and James F. Gusella and Christine Klein and Giorgio Casari and Alessandro De Grandi and Peter Paul Pramstaller},
  journal={American journal of human genetics},
  year={2006},
  volume={79 4},
  pages={
          716-23
        }
}
Restless legs syndrome (RLS) is a common neurological condition with three loci (12q, 14q, and 9p) described so far, although none of these genes has yet been identified. We report a genomewide linkage scan of patients with RLS (n=37) assessed in a population isolate (n=530) of South Tyrol (Italy). Using both nonparametric and parametric analyses, we initially obtained suggestive evidence of a novel locus on chromosome 2q, with nominal evidence of linkage on chromosomes 5p and 17p. Follow-up… 

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...

References

SHOWING 1-10 OF 36 REFERENCES

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

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.

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.

Restless legs syndrome: confirmation of linkage to chromosome 12q, genetic heterogeneity, and evidence of complexity.

The results support the presence of a major restless legs syndrome-susceptibility locus on chromosome 12q, which has been designated as RLS1, and suggest that at least one additional locus may be involved in the origin of this prevalent condition.

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.

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

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.

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.

Autosomal dominant restless legs syndrome maps on chromosome 14q.

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.

The 14q restless legs syndrome locus in the French Canadian population

A new restless legs syndrome locus on chromosome 14 recently has been reported in one family of Italian origin, providing support for the existence of this locus and indicating thatThis locus may be responsible for a small fraction of French Canadian restless Legs syndrome.

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.

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.