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Nonsyndromic Hearing Loss Caused by USH1G Mutations: Widening the USH1G Disease Spectrum

Maria Oonk, Anne Marthe1,2; van Huet, Ramon A. C.3; Leijendeckers, Joop M.1,2; Oostrik, Jaap1,2,4; Venselaar, Hanka5; van Wijk, Erwin1,2,4; Beynon, Andy1,2; Kunst, Henricus P. M.1,2; Hoyng, Carel B.3; Kremer, Hannie1,2,4,6; Schraders, Margit1,2,4; Pennings, Ronald J. E.1,2

doi: 10.1097/AUD.0000000000000095
Research Articles

Objective: Currently, six genes are known to be associated with Usher syndrome type I, and mutations in most of these genes can also cause nonsyndromic hearing loss. The one exception is USH1G, which is currently only known to be involved in Usher syndrome type I and atypical Usher syndrome.

Design: A Dutch family with autosomal recessively inherited hearing loss was examined. Audiometric, ophthalmic, and vestibular evaluations were performed besides the genetic analysis.

Results: The hearing loss had an early onset with a downsloping audiogram configuration. Slight progression of the hearing loss was seen in both affected individuals. Compound heterozygous mutations in USH1G were found to segregate with the hearing loss in this family, a missense (c.310A>G, p.Met104Val) and a frameshift mutation (c.780insGCAC, p.Tyr261Alafs*96). Extensive ophthalmic and vestibular examinations demonstrated no abnormalities that are usually associated with Usher syndrome type I.

Conclusions: This is the first family presented with nonsyndromic hearing loss caused by mutations in USH1G. Our findings expand the phenotypic spectrum of mutations in USH1G.

We present a Dutch family with autosomal recessively inherited hearing loss. The hearing loss has an early onset with a downsloping audiogram configuration. Slight progression of the hearing loss is seen in both affected individuals. Missense (c.310A>G, p.Met104Val) and frameshift (c.780insGCAC, p.Tyr261Alafs*96) mutations in USH1G are found to segregate with the hearing loss in this family. Extensive ophthalmic and vestibular examinations demonstrate no abnormalities that are usually associated with Usher syndrome type I. This is the first family presented with nonsyndromic hearing loss caused by mutations in USH1G. Our findings expand the phenotypic spectrum of mutations in USH1G.

1Department of Otorhinolaryngology, Hearing and Genes, Radboud University Medical Center, Nijmegen, The Netherlands; 2Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, The Netherlands; 3Department of Ophthalmology, Radboud University Medical Center, Nijmegen, The Netherlands; 4Nijmegen Centre for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands; 5Centre for Molecular and Biomolecular Informatics, Radboud University Medical Center, Nijmegen, The Netherlands; and 6Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.

This work was funded by the Heinsius Houbolt Foundation (H.K.), the Oticon Foundation (09-3742 to H.K.), ZonMW (40-00812-98-09047 to H.K. and 90700388 to R.J.E.P.), and the Stichting A.F. Deutman Researchfonds Oogheelkunde, Nijmegen (C.B.H. and R.A.C.H.). For the remaining authors, none was declared.

The authors declare no other conflict of interest.

Address for correspondence: A. M. M. Oonk, MD, Department of Otorhinolaryngology, Radboud University Medical Center, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands. E-mail: Anne.Oonk@radboudumc.nl

Received February 2, 2014; accepted July 13, 2014.

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