Evidence for linkage of restless legs syndrome to chromosome 9p: are there two distinct loci?

K. Lohmann-Hedrich, A. Neumann, A. Kleensang, T. Lohnau, H. Muhle, A. Djarmati, I. R. König, P. P. Pramstaller, E. Schwinger, P. L. Kramer, A. Ziegler, U. Stephani, C. Klein

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Abstract

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 microsatellite markers at the five known loci. Prompted by the identification of a potentially shared haplotype near the RLS3 locus, we expanded the investigated linkage region on chromosome 9p using additional DNA markers. RESULTS: Mode of inheritance in our RLS family was compatible with an autosomal dominant pattern, and disease onset was mainly in childhood or adolescence. We excluded linkage to the RLS1, RLS2, RLS4, and RLS5 loci. However, we identified a likely new RLS gene locus (RLS3*) on chromosome 9p with a maximum lod score of 3.60 generated by model-based multipoint linkage analysis. A haplotype flanked by D9S974 and D9S1118 in a 9.9-Mb region, centromeric to RLS3, was shared by all 12 investigated patients. In addition, 11 of them carried a common haplotype extending telomeric to D9S2189 that is located within RLS3. CONCLUSIONS: We demonstrate linkage to a locus on chromosome 9p that is probably distinct from RLS3. Our 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.

Original languageEnglish (US)
Pages (from-to)686-694
Number of pages9
JournalNeurology
Volume70
Issue number9
DOIs
StatePublished - Feb 26 2008
Externally publishedYes

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Restless Legs Syndrome
Chromosomes
Haplotypes
Sensation Disorders
Genes
Lod Score
Paresthesia
Genetic Markers
Microsatellite Repeats
Leg
Phenotype
Mutation

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Lohmann-Hedrich, K., Neumann, A., Kleensang, A., Lohnau, T., Muhle, H., Djarmati, A., ... Klein, C. (2008). Evidence for linkage of restless legs syndrome to chromosome 9p: are there two distinct loci? Neurology, 70(9), 686-694. https://doi.org/10.1212/01.wnl.0000282760.07650.ba

Evidence for linkage of restless legs syndrome to chromosome 9p : are there two distinct loci? / Lohmann-Hedrich, K.; Neumann, A.; Kleensang, A.; Lohnau, T.; Muhle, H.; Djarmati, A.; König, I. R.; Pramstaller, P. P.; Schwinger, E.; Kramer, P. L.; Ziegler, A.; Stephani, U.; Klein, C.

In: Neurology, Vol. 70, No. 9, 26.02.2008, p. 686-694.

Research output: Contribution to journalArticle

Lohmann-Hedrich, K, Neumann, A, Kleensang, A, Lohnau, T, Muhle, H, Djarmati, A, König, IR, Pramstaller, PP, Schwinger, E, Kramer, PL, Ziegler, A, Stephani, U & Klein, C 2008, 'Evidence for linkage of restless legs syndrome to chromosome 9p: are there two distinct loci?', Neurology, vol. 70, no. 9, pp. 686-694. https://doi.org/10.1212/01.wnl.0000282760.07650.ba
Lohmann-Hedrich K, Neumann A, Kleensang A, Lohnau T, Muhle H, Djarmati A et al. Evidence for linkage of restless legs syndrome to chromosome 9p: are there two distinct loci? Neurology. 2008 Feb 26;70(9):686-694. https://doi.org/10.1212/01.wnl.0000282760.07650.ba
Lohmann-Hedrich, K. ; Neumann, A. ; Kleensang, A. ; Lohnau, T. ; Muhle, H. ; Djarmati, A. ; König, I. R. ; Pramstaller, P. P. ; Schwinger, E. ; Kramer, P. L. ; Ziegler, A. ; Stephani, U. ; Klein, C. / Evidence for linkage of restless legs syndrome to chromosome 9p : are there two distinct loci?. In: Neurology. 2008 ; Vol. 70, No. 9. pp. 686-694.
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abstract = "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 microsatellite markers at the five known loci. Prompted by the identification of a potentially shared haplotype near the RLS3 locus, we expanded the investigated linkage region on chromosome 9p using additional DNA markers. RESULTS: Mode of inheritance in our RLS family was compatible with an autosomal dominant pattern, and disease onset was mainly in childhood or adolescence. We excluded linkage to the RLS1, RLS2, RLS4, and RLS5 loci. However, we identified a likely new RLS gene locus (RLS3*) on chromosome 9p with a maximum lod score of 3.60 generated by model-based multipoint linkage analysis. A haplotype flanked by D9S974 and D9S1118 in a 9.9-Mb region, centromeric to RLS3, was shared by all 12 investigated patients. In addition, 11 of them carried a common haplotype extending telomeric to D9S2189 that is located within RLS3. CONCLUSIONS: We demonstrate linkage to a locus on chromosome 9p that is probably distinct from RLS3. Our 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.",
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T1 - Evidence for linkage of restless legs syndrome to chromosome 9p

T2 - are there two distinct loci?

AU - Lohmann-Hedrich, K.

AU - Neumann, A.

AU - Kleensang, A.

AU - Lohnau, T.

AU - Muhle, H.

AU - Djarmati, A.

AU - König, I. R.

AU - Pramstaller, P. P.

AU - Schwinger, E.

AU - Kramer, P. L.

AU - Ziegler, A.

AU - Stephani, U.

AU - Klein, C.

PY - 2008/2/26

Y1 - 2008/2/26

N2 - 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 microsatellite markers at the five known loci. Prompted by the identification of a potentially shared haplotype near the RLS3 locus, we expanded the investigated linkage region on chromosome 9p using additional DNA markers. RESULTS: Mode of inheritance in our RLS family was compatible with an autosomal dominant pattern, and disease onset was mainly in childhood or adolescence. We excluded linkage to the RLS1, RLS2, RLS4, and RLS5 loci. However, we identified a likely new RLS gene locus (RLS3*) on chromosome 9p with a maximum lod score of 3.60 generated by model-based multipoint linkage analysis. A haplotype flanked by D9S974 and D9S1118 in a 9.9-Mb region, centromeric to RLS3, was shared by all 12 investigated patients. In addition, 11 of them carried a common haplotype extending telomeric to D9S2189 that is located within RLS3. CONCLUSIONS: We demonstrate linkage to a locus on chromosome 9p that is probably distinct from RLS3. Our 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.

AB - 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 microsatellite markers at the five known loci. Prompted by the identification of a potentially shared haplotype near the RLS3 locus, we expanded the investigated linkage region on chromosome 9p using additional DNA markers. RESULTS: Mode of inheritance in our RLS family was compatible with an autosomal dominant pattern, and disease onset was mainly in childhood or adolescence. We excluded linkage to the RLS1, RLS2, RLS4, and RLS5 loci. However, we identified a likely new RLS gene locus (RLS3*) on chromosome 9p with a maximum lod score of 3.60 generated by model-based multipoint linkage analysis. A haplotype flanked by D9S974 and D9S1118 in a 9.9-Mb region, centromeric to RLS3, was shared by all 12 investigated patients. In addition, 11 of them carried a common haplotype extending telomeric to D9S2189 that is located within RLS3. CONCLUSIONS: We demonstrate linkage to a locus on chromosome 9p that is probably distinct from RLS3. Our 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.

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