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

  title={Evidence for further genetic locus heterogeneity and confirmation of RLS‐1 in restless legs syndrome},
  author={Juliane Winkelmann and Peter Lichtner and Benno P{\"u}tz and Claudia Trenkwalder and Stephanie Hauk and Thomas Meitinger and Tim Matthias Strom and Bertram Muller-Myhsok},
  journal={Movement Disorders},
Restless legs syndrome (RLS; MIM 102300) is a common neurological disorder characterized by dysesthesias and an urge to move the lower limbs. The symptoms predominantly occur at rest, in the evening, and improve with movement. There is a high familial aggregation but gene mutations have not yet been found. Three loci for RLS on chromosomes 12q, 14q, and 9p (RLS‐1, RLS‐2, and RLS‐3) have been reported with a recessive (RLS‐1) and autosomal dominant (RLS‐2, RLS‐3) mode of inheritance… 

Evidence for linkage of restless legs syndrome to chromosome 9p

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.

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

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

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.

A novel locus for restless legs syndrome maps to chromosome 19p in an Irish pedigree

A genome-wide linkage analysis in an Irish autosomal dominant RLS pedigree with 11 affected members provides evidence of a novel RLS locus and provides further evidence that RLS is a genetically heterogenous disorder.

[Advances in genetics of restless legs syndrome].

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%.

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.

Restless legs syndrome: an update on genetics and future perspectives

The molecular findings, together with the variable expressivity of the phenotype, suggest a substantial clinical and genetic heterogeneity of RLS, which is consistent with a common, underdiagnosed neurological condition.

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.

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.

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

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.



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.

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.

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.

Clinical characteristics and frequency of the hereditary restless legs syndrome in a population of 300 patients.

It is shown that patients with hereditary RLS may experience an earlier onset of the disease, compared to those of non-hereditary RLS, which was similar in both groups.

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.

Toward a better definition of the restless legs syndrome

Features commonly seen in RLS include sleep disturbance, periodic limb movements in sleep and similar involuntary movements while awake, a normal neurological examination in the idiopathic from, a tendency for the symptoms to be worse in middle to older age, and, in some cases, a family history suggestive of an autosomal dominant mode of inheritance.

Sex and the risk of restless legs syndrome in the general population.

Restless legs syndrome is a common disease in the general population, affecting women more often than men, and is associated with reduced quality of life in cross-sectional analysis.

Clinical, polysomnographic, and genetic characteristics of restless legs syndrome: A study of 133 patients diagnosed with new standard criteria

A strong relationship was found between these complaints and polysomnographic findings; increasing sleep latency and number of awakenings and decreasing sleep efficiency were associated with worsening symptoms.

A questionnaire study of 138 patients with restless legs syndrome

A telephone survey of their symptomatology found that more than a third of the patients in each group experienced their first symptoms before the age of 20 and in the older age-onset patients, misdiagnoses also included skin irritation, arthritis, and malingering.

Reply to Kock et al.

The published version of the original article reporting linkage between RLS and a locus on chromosome 12q contained an error that will clarify the issue pertaining to the model raised by Kock et al., since their criticisms were based on misinterpretations induced by this unfortunate error.