title: Dysferlinopathy in Switzerland: clinical phenotypes and potential founder effects.
abstract: BACKGROUND
  Dysferlin is reduced in patients with limb girdle muscular dystrophy type 2B, Miyoshi myopathy, distal anterior compartment myopathy, and in certain Ethnic clusters.
  
  
  METHODS
  We evaluated clinical and genetic patient data from three different Swiss Neuromuscular Centers.
  
  
  RESULTS
  Thirteen patients from 6 non-related families were included. Age of onset was 18.8 ± 4.3 years. In all patients, diallelic disease-causing mutations were identified in the DYSF gene. Nine patients from 3 non-related families from Central Switzerland carried the identical homozygous mutation, c.3031 + 2 T>C. A possible founder effect was confirmed by haplotype analysis. Three patients from two different families carried the heterozygous mutation, c.1064_1065delAA. Two novel mutations were identified (c.2869 C>T (p.Gln957Stop), c.5928 G>A (p.Trp1976Stop)).
  
  
  CONCLUSIONS
  Our study confirms the phenotypic heterogeneity associated with DYSF mutations. Two mutations (c.3031 + 2 T>C, c.1064_1065delAA) appear common in Switzerland. Haplotype analysis performed on one case (c. 3031 + 2 T>C) suggested a possible founder effect.
authors.affiliation: Department of Neurology, University Hospital Zürich, Frauenklinikstrasse 26, 8091, Zürich, Switzerland. jens.petersen@usz.ch.
authors.forename: Jens A
authors.initials: JA
authors.lastname: Petersen
authors.affiliation: Nerve-Muscle Unit, Neurology Service, Department of Clinical Neurosciences, Lausanne University Hospital (CHUV), Lausanne, Switzerland. Thierry.Kuntzer@chuv.ch.
authors.forename: Thierry
authors.initials: T
authors.lastname: Kuntzer
authors.affiliation: Department of Neurology, University Hospital Basel, Basel, Switzerland. dirk.fischer@ukbb.ch.
authors.forename: Dirk
authors.initials: D
authors.lastname: Fischer
authors.affiliation: Abteilung Neuropäriatrie, Dresden, Germany. maja.v.d.hagen@uniklinikum-dresden.de.
authors.forename: Maja
authors.initials: M
authors.lastname: von der Hagen
authors.affiliation: Klinik für Kinder- und Jugendmedizin, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany. Angela.Huebner@uniklinikum-dresden.de.
authors.forename: Angela
authors.initials: A
authors.lastname: Huebner
authors.affiliation: Institute of Neuropathology, University Hospital Zürich, Zürich, Switzerland. veronika.kana@usz.ch.
authors.forename: Veronika
authors.initials: V
authors.lastname: Kana
authors.affiliation: Department of Pathology, University Hospital Geneva, Geneva, Switzerland. Johannes.A.Lobrinus@hcuge.ch.
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Lobrinus
authors.affiliation: Institure of Human Genetics, University of Würzburg, Würzburg, Germany. wkress@biozentrum.uni-wuerzburg.de.
authors.forename: Wolfram
authors.initials: W
authors.lastname: Kress
authors.affiliation: Institute of Neuropathology, University Hospital Zürich, Zürich, Switzerland. ElisabethJane.Rushing@usz.ch.
authors.forename: Elisabeth J
authors.initials: EJ
authors.lastname: Rushing
authors.affiliation: Department of Neurology, University Hospital Basel, Basel, Switzerland. MSinnreich@uhbs.ch.
authors.forename: Michael
authors.initials: M
authors.lastname: Sinnreich
authors.affiliation: Department of Neurology, University Hospital Zürich, Frauenklinikstrasse 26, 8091, Zürich, Switzerland. hans.jung@usz.ch.
authors.forename: Hans H
authors.initials: HH
authors.lastname: Jung
mesh_terms: D000293:Adolescent; D000328:Adult; D000073939:Dysferlin; D005260:Female; D018703:Founder Effect; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics*; D049288:Muscular Dystrophies, Limb-Girdle / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D013557:Switzerland; D055815:Young Adult
chemical_list: C114839:DYSF protein, human; D000073939:Dysferlin; D008565:Membrane Proteins; D009124:Muscle Proteins