A Novel Locus for Restless Legs Syndrome on Chromosome 13q

Balaban, Hatice; Bayraklı, Fatih; Kartal, Ugur; Pınarbaşı, Ergün; Topaktaş, Suat; Kars, H Z

doi:10.1159/000338779

Cited by 13 publications

(4 citation statements)

References 55 publications

(41 reference statements)

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“…Current theories of RLS pathophysiology emphasize brain iron deficiency with abnormal dopaminergic consequences, together with a strong underlying genetic background (reviewed in Dauvilliers and Winkelmann, 2013). A recent study analyzing 11 individuals from the same family indicated the existence of a locus on chromosome 13q, between SNPs rs2182885 and rs7333498 (around 5.3 Mb in size; Balaban et al, 2012). The NALCN gene lies in this region.…”

Section: Possible Implications Of Nalcn In Human Diseasesmentioning

confidence: 99%

The sodium leak channel, NALCN, in health and disease

Cochet-Bissuel

Lory

Monteil

2014

Front. Cell. Neurosci.

118

122

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Ion channels are crucial components of cellular excitability and are involved in many neurological diseases. This review focuses on the sodium leak, G protein-coupled receptors (GPCRs)-activated NALCN channel that is predominantly expressed in neurons where it regulates the resting membrane potential and neuronal excitability. NALCN is part of a complex that includes not only GPCRs, but also UNC-79, UNC-80, NLF-1 and src family of Tyrosine kinases (SFKs). There is growing evidence that the NALCN channelosome critically regulates its ion conduction. Both in mammals and invertebrates, animal models revealed an involvement in many processes such as locomotor behaviors, sensitivity to volatile anesthetics, and respiratory rhythms. There is also evidence that alteration in this NALCN channelosome can cause a wide variety of diseases. Indeed, mutations in the NALCN gene were identified in Infantile Neuroaxonal Dystrophy (INAD) patients, as well as in patients with an Autosomal Recessive Syndrome with severe hypotonia, speech impairment, and cognitive delay. Deletions in NALCN gene were also reported in diseases such as 13q syndrome. In addition, genes encoding NALCN, NLF- 1, UNC-79, and UNC-80 proteins may be susceptibility loci for several diseases including bipolar disorder, schizophrenia, Alzheimer's disease, autism, epilepsy, alcoholism, cardiac diseases and cancer. Although the physiological role of the NALCN channelosome is poorly understood, its involvement in human diseases should foster interest for drug development in the near future. Toward this goal, we review here the current knowledge on the NALCN channelosome in physiology and diseases.

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Section: Possible Implications Of Nalcn In Human Diseasesmentioning

confidence: 99%

The sodium leak channel, NALCN, in health and disease

Cochet-Bissuel

Lory

Monteil

2014

Front. Cell. Neurosci.

118

122

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“…Other factors include iron deficiency, dysfunctions of the tyrosine kinase and peripheral neuronal sensitization 5 . The first genetic locus associated with RLS was mapped to chromosome 12q, and five other loci have been described (13q, 14q, 9p, 2q, 20p) [9][10][11] .…”

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confidence: 99%

Comorbidities, medications and depressive symptoms in patients with restless legs syndrome and migraine

Ferreira

Éckeli

Dach

et al. 2013

Arq. Neuro-Psiquiatr.

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OBJECTIVE: The pathophysiology of migraine and restless legs syndrome (RLS) seems to involve inherited mechanism and dysfunction of the dopaminergic system. Previous articles have shown that the frequency of RLS is higher in migraine patients than in controls. We conducted a study to evaluate comorbidities, medication used and depressive symptoms that can explain the relation between migraine and RLS. METHODS: A case-control study was performed in which patients with migraine (n=72) and a control group without migraine (n=72) were interviewed. Data including RLS diagnosis, depressive symptoms, comorbidities and drugs used were evaluated. RESULTS: There was a significant association between migraine and RLS (p=0.01), but comorbidities such as diabetes, hypertension, anemia and drugs used did not explain this association. Depression scores, as measured by the Beck Depression Inventory, were higher in migraine patients with RLS (p =0.04). CONCLUSION: No specific factors explaining the association between migraine and RLS were found. Symptoms of depression were more frequent in patients with migraine and RLS.

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“…6 In some cases, RLS may be caused by an underlying disease (iron deficiency anemia, end-stage chronic renal disease, peripheral neuropathy), but it is usually an idiopathic disorder for which the etiology is uncertain, although genetic factors are known to be involved. [7][8][9][10][11][12][13][14][15][16] Quality of life is greatly reduced by RLS, as much as in other chronic diseases like diabetes or depression. 6,17,18 Prospective data have shown that women with RLS are at higher risk of developing clinical depression.…”

Section: Clinical Features and Diagnosismentioning

confidence: 99%

The status of rotigotine as a safe and effective alternative in the treatment of restless legs syndrome

Bourgeois¹,

Frénette²

2013

RRTD

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Restless legs syndrome (RLS) is characterized by an urge to move the legs that occurs mainly with inactivity, and it is relieved by movement and is usually worse by the end of the day. It is highly prevalent, affecting 1.9% to 4.5% of the population, and although its etiology is uncertain, genetic factors seem to be involved. When symptoms are severe enough to warrant chronic therapy, dopamine receptor agonists are to be considered for initial treatment. Rotigotine, the most recently developed drug in this category, is the only one available for transdermal delivery in RLS. It was initially designed for the treatment of Parkinson's disease. The US Food and Drug Administration approved its use in cases of moderate to severe RLS in April 2012. Its efficacy has been well established in randomized placebo-controlled trials, as it appears to be especially useful in patients with daily symptoms. The most commonly reported side effect is local skin reaction. Complications such as augmentation, somnolence, or compulsive behavior may happen, although they seldom occur. The American Academy of Sleep Medicine clinical practice guideline recommends a "Guideline Level" for rotigotine, and European RLS guidelines provide a "level A" recommendation for short-term therapy; it also was the only dopaminergic agonist considered to be effective for the long-term management of RLS.

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A Novel Locus for Restless Legs Syndrome on Chromosome 13q

Cited by 13 publications

References 55 publications

The sodium leak channel, NALCN, in health and disease

The sodium leak channel, NALCN, in health and disease

Comorbidities, medications and depressive symptoms in patients with restless legs syndrome and migraine

The status of rotigotine as a safe and effective alternative in the treatment of restless legs syndrome

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