Open AccessUsher syndrome in Denmark: mutation spectrum and some clinical observations
Author(s) -
Dad Shzeena,
Rendtorff Nanna Dahl,
Tranebjærg Lisbeth,
Grønskov Karen,
Karstensen Helena Gásdal,
Brox Vigdis,
Nilssen Øivind,
Roux AnneFrançoise,
Rosenberg Thomas,
Jensen Hanne,
Møller Lisbeth Birk
Publication year - 2016
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.228
Subject(s) - usher syndrome , biology , genetics , sanger sequencing , mutation , genetic heterogeneity , retinitis pigmentosa , gene , phenotype
Background Usher syndrome ( USH ) is a genetically heterogeneous deafness‐blindness syndrome, divided into three clinical subtypes: USH 1, USH 2 and USH 3. 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 USH 1, 7 USH 2, 1 USH 3) were identified by Sanger sequencing of USH 1C , USH 2A or CLRN 1 or by Arrayed Primer EX tension ( APEX ) method. Mutations in 12 individuals (7 USH 1, 5 USH 2) 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 USH 1, 67 with USH 2, and 1 with USH 3. 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. Conclusion Mutations that lead to USH 1 were predominantly identified in MYO 7A (75%), whereas all mutations in USH 2 cases were identified in USH 2A . The MYO 7A mutation c.93C>A, p.(Cys31*) accounted for 33% of all USH 1 mutations and the USH 2A c.2299delG, p.(Glu767Serfs*21) variant accounted for 45% of all USH 2 mutations in the Danish cohort.