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Phenotypic Characterization of DFNB16-associated Hearing Loss

Back, Daniela*; Shehata-Dieler, Wafaa*; Vona, Barbara; Hofrichter, Michaela A. H.; Schroeder, Joerg; Haaf, Thomas; Rahne, Torsten; Hagen, Rudolf*; Schraven, Sebastian P.§

doi: 10.1097/MAO.0000000000002059
PEDIATRIC OTOLOGY

Hypothesis: We hypothesized that patients with DFNB16 caused hearing loss show characteristical audiological findings depending on genetic results.

Background: Hearing loss belongs to the most frequent congenital diseases. In 50–70% of individuals, hearing loss is caused by genetic defects. DFNB1 (deafness, neurosensory, autosomal-recessive) is the most frequently affected locus. Despite its great genetic heterogeneity, comprehensive analysis of genes like STRC, encoding stereocilin (DFNB16) is possible. The genetic architecture of the DFNB16 locus is challenging and requires a unique molecular genetic testing assay. The aim of the study is a systematic characterization of the audiological phenotype in DFNB16-positive patients.

Methods: Since 2011, 290 patients with suspicion of inherited hearing loss received a human genetic exploration. Eighty two DFNB1-negative patients advanced to further testing in the DFNB16 locus. STRC-positive patients obtained complete audiological diagnostic workup. Additionally, epidemiological data was collected.

Results: Nine of 82 (11%) of the examined patients (mean age 5 yr) showed mutations in the STRC (3 homozygous, 6 compound heterozygous). Aside from a moderate hearing loss in the pure tone audiogram, auditory brainstem response thresholds were 40–50 dB nHL. Otoacoustic emissions were detectable in only one patient.

Conclusions: Examination of the DFNB16-locus should be a standard diagnostic test after negative DFNB1-gene screening result. Notably, DFNB16-associated hearing loss can be audiologically characterized as moderate sensorineural hearing loss in the main speech field with absent otoacoustic emissions. Our study is the first to correlate audiological findings with genetic results in patients with hearing loss due to STRC.

*Department of Oto-Rhino-Laryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, Comprehensive Hearing Center, University Hospital Würzburg

Institute of Human Genetics, University of Würzburg, Biozentrum, Würzburg, Germany

Department of Otorhinolaryngology, Head and Neck Surgery, University of Halle-Wittenberg, Halle (Saale)

§Department of Oto-Rhino-Laryngology, Head and Neck Surgery “Otto Körner”, University Hospital Rostock, Rostock, Germany

Address correspondence and reprint requests to Daniela Back, M.D., Department of Oto-Rhino-Laryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, Comprehensive Hearing Center, University Hospital Würzburg, Josef-Schneider-Straße 11, D-97080 Würzburg, Germany; E-mail: back_d@ukw.de

D.B. and W. S.-D. These authors contributed equally to this work.

Disclosure of Funding: none.

Author's roles:

Dr. med. Daniela Back: Conceptualization, data administration, formal analysis, methodology, writing – original draft, and writing – review and editing.

Prof. Dr. med./ET Wafaa Shehata-Dieler: Conceptualization, investigation, supervision, validation, and writing – review and editing.

Dr. rer. nat. Barbara Vona: Genetic investigation, visualization, data administration, and writing – review and editing.

Michaela A. H. Hofrichter: Genetic investigation and data administration.

Dr. med. Joerg Schroeder: Patient recruitment.

Univ. Prof. Dr. Thomas Haaf: Data administration, genetic investigation, supervision.

Apl. Prof. Dr. rer. nat., rer. medic. habil. Torsten Rahne: Visualization.

Univ.- Prof. Dr. med. Dr. h.c. Rudolf Hagen: Writing – review and editing.

Priv. -Doz. Dr. med. Sebastian Philipp Schraven: Conceptualization, data administration, formal analysis, supervision, methodology, and writing – review and editing.

The authors disclose no conflicts of interest.

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