Secondary Logo

Institutional members access full text with Ovid®

Genetics of Usher Syndrome

New Insights From a Meta-analysis

Jouret, Guillaume*; Poirsier, Céline*; Spodenkiewicz, Marta*; Jaquin, Clémence*; Gouy, Evan*; Arndt, Carl; Labrousse, Marc; Gaillard, Dominique*; Doco-Fenzy, Martine*; Lebre, Anne-Sophie*

doi: 10.1097/MAO.0000000000002054

Objective: To describe the genetic and phenotypic spectrum of Usher syndrome after 6 years of studies by next-generation sequencing, and propose an up-to-date classification of Usher genes in patients with both visual and hearing impairments suggesting Usher syndrome, and in patients with seemingly isolated deafness.

Study Design: The systematic review and meta-analysis protocol was based on Cochrane and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We performed 1) a meta-analysis of data from 11 next-generation sequencing studies in 684 patients with Usher syndrome; 2) a meta-analysis of data from 21 next-generation studies in 2,476 patients with seemingly isolated deafness, to assess the involvement of Usher genes in seemingly nonsyndromic hearing loss, and thus the proportion of patients at high risk of subsequent retinitis pigmentosa (RP); 3) a statistical analysis of differences between parts 1) and 2).

Results: In patients with both visual and hearing impairments, the biallelic disease-causing mutation rate was assessed for each Usher gene to propose a classification by frequency: USH2A: 50% (341/684) of patients, MYO7A: 21% (144/684), CDH23: 6% (39/684), ADGRV1: 5% (35/684), PCDH15: 3% (21/684), USH1C: 2% (17/684), CLRN1: 2% (14/684), USH1G: 1% (9/684), WHRN: 0.4% (3/684), PDZD7 0.1% (1/684), CIB2 (0/684). In patients with seemingly isolated sensorineural deafness, 7.5% had disease-causing mutations in Usher genes, and are therefore at high risk of developing RP. These new findings provide evidence that usherome dysfunction is the second cause of genetic sensorineural hearing loss after connexin dysfunction.

Conclusion: These results promote generalization of early molecular screening for Usher syndrome in deaf children.

*Department of Genetics

Department of Ophtalmology

Department of Otorhinolaryngology, Reims University Hospital, Reims, France

Address correspondence and reprint requests to Guillaume Jouret, M.D., M.Sc., Service de Génétique, American Memorial Hospital, Hôpital d’Enfants, Centre Hospitalo-Universitaire de Reims, 47 Rue Cognacq-Jay 51100 REIMS Cedex, France; E-mail:

The authors declare that the study was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflicts of interest.

Copyright © 2019 by Otology & Neurotology, Inc. Image copyright © 2010 Wolters Kluwer Health/Anatomical Chart Company