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Exome sequencing in a family with restless legs syndrome
Author(s) -
Weissbach Anne,
Siegesmund Katharina,
Brüggemann Norbert,
Schmidt Alexander,
Kasten Meike,
Pichler Irene,
Muhle Hiltrud,
Lohmann Ebba,
Lohnau Thora,
Schwinger Eberhard,
Hagenah Johann,
Stephani Ulrich,
Pramstaller Peter P.,
Klein Christine,
Lohmann Katja
Publication year - 2012
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.25191
Subject(s) - missense mutation , genetics , exome sequencing , exon , biology , genetic linkage , candidate gene , gene , exome , mutation
Background: Restless legs syndrome (RLS) has a high familial aggregation. To date, several loci and genetic risk factors have been identified, but no causative gene mutation has been found. Methods: We evaluated a German family with autosomal dominantly inherited RLS in 7 definitely and 2 possibly affected members by genome‐wide linkage analysis and exome sequencing. Results: We identified three novel missense and one splice site variant in the PCDHA3 , WWC2 , ATRN , and FAT2 genes that segregated with RLS in the family. All four exons of the PCDHA3 gene, the most plausible candidate, were sequenced in 64 unrelated RLS cases and 250 controls. This revealed three additional rare missense variants (frequency <1%) of unknown pathogenicity in 2 patients and 1 control. Conclusions: We present the first next‐generation sequencing study on RLS and suggest PCDHA3 as a candidate gene for RLS. © 2012 Movement Disorder Society