title: Usher syndrome in Denmark: mutation spectrum and some clinical observations.
abstract: BACKGROUND
  Usher syndrome (USH) is a genetically heterogeneous deafness-blindness syndrome, divided into three clinical subtypes: USH1, USH2 and USH3.
  
  
  METHODS
  Mutations in 21 out of 26 investigated Danish unrelated individuals with USH were identified, using a combination of molecular diagnostic methods.
  
  
  RESULTS
  Before Next Generation Sequencing (NGS) became available mutations in nine individuals (1 USH1, 7 USH2, 1 USH3) were identified by Sanger sequencing ofUSH1C,USH2AorCLRN1or by Arrayed Primer EXtension (APEX) method. Mutations in 12 individuals (7 USH1, 5 USH2) were found by targeted NGS of ten known USH genes. Five novel pathogenic variants were identified. We combined our data with previously published, and obtained an overview of the USH mutation spectrum in Denmark, including 100 unrelated individuals; 32 with USH1, 67 with USH2, and 1 with USH3. Macular edema was observed in 44 of 117 individuals. Olfactory function was tested in 12 individuals and found to be within normal range in all.
  
  
  CONCLUSIONS
  Mutations that lead to USH1 were predominantly identified inMYO7A(75%), whereas all mutations in USH2 cases were identified inUSH2A. TheMYO7Amutation c.93C>A, p.(Cys31*) accounted for 33% of all USH1 mutations and theUSH2Ac.2299delG, p.(Glu767Serfs*21) variant accounted for 45% of all USH2 mutations in the Danish cohort.
authors.affiliation: Applied Human Genetics Kennedy Center Department of Clinical Genetics Copenhagen University Rigshospitalet Glostrup Denmark.
authors.forename: Shzeena
authors.initials: S
authors.lastname: Dad
authors.affiliation: Applied Human GeneticsKennedy CenterDepartment of Clinical GeneticsCopenhagen UniversityRigshospitaletGlostrupDenmark; Department of Cellular and Molecular MedicineThe Faculty of Health SciencesUniversity of Copenhagen2200CopenhagenDenmark; Department of Otorhinolaryngology, Head & Neck Surgery and AudiologyBispebjerg Hospital/RigshospitaletCopenhagenDenmark.
authors.forename: Nanna Dahl
authors.initials: ND
authors.lastname: Rendtorff
authors.affiliation: Applied Human GeneticsKennedy CenterDepartment of Clinical GeneticsCopenhagen UniversityRigshospitaletGlostrupDenmark; Department of Cellular and Molecular MedicineThe Faculty of Health SciencesUniversity of Copenhagen2200CopenhagenDenmark; Department of Otorhinolaryngology, Head & Neck Surgery and AudiologyBispebjerg Hospital/RigshospitaletCopenhagenDenmark.
authors.forename: Lisbeth
authors.initials: L
authors.lastname: Tranebjærg
authors.affiliation: Applied Human GeneticsKennedy CenterDepartment of Clinical GeneticsCopenhagen UniversityRigshospitaletGlostrupDenmark; Department of Cellular and Molecular MedicineThe Faculty of Health SciencesUniversity of Copenhagen2200CopenhagenDenmark.
authors.forename: Karen
authors.initials: K
authors.lastname: Grønskov
authors.affiliation: Department of Cellular and Molecular Medicine The Faculty of Health Sciences University of Copenhagen 2200 Copenhagen Denmark.
authors.forename: Helena Gásdal
authors.initials: HG
authors.lastname: Karstensen
authors.affiliation: Department of Medical Genetics University Hospital of North-Norway N-9038 Tromsø Norway.
authors.forename: Vigdis
authors.initials: V
authors.lastname: Brox
authors.affiliation: Department of Medical GeneticsUniversity Hospital of North-NorwayN-9038TromsøNorway; Department of Clinical Medicine, Medical GeneticsUniversity of TromsøNO-9037TromsøNorway.
authors.forename: Øivind
authors.initials: Ø
authors.lastname: Nilssen
authors.affiliation: Laboratoire de Génétique MoléculaireCHU MontpellierMontpellierF-34000France; U827InsermMontpellierF-34000France.
authors.forename: Anne-Françoise
authors.initials: AF
authors.lastname: Roux
authors.affiliation: The National Eye ClinicThe Kennedy CenterDepartment of OphthalmologyCopenhagen University Hospital2600RigshospitaletGlostrupDenmark; Institute of Clinical MedicineThe Faculty of Health SciencesUniversity of Copenhagen2200Copenhagen NDenmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Rosenberg
authors.affiliation: The National Eye Clinic The Kennedy Center Department of Ophthalmology Copenhagen University Hospital 2600 Rigshospitalet Glostrup Denmark.
authors.forename: Hanne
authors.initials: H
authors.lastname: Jensen
authors.affiliation: Applied Human GeneticsKennedy CenterDepartment of Clinical GeneticsCopenhagen UniversityRigshospitaletGlostrupDenmark; Department of Cellular and Molecular MedicineThe Faculty of Health SciencesUniversity of Copenhagen2200CopenhagenDenmark; Department of Science Systems and Models (NSM)Roskilde UniversityDK 4000RoskildeDenmark.
authors.forename: Lisbeth Birk
authors.initials: LB
authors.lastname: Møller
keywords: Cataract; Denmark; Usher syndrome; macular edema; mutation; olfactory function; targeted NGS