Daniela Back1, Wafaa Shehata-Dieler1, Barbara Vona2, Michaela A H Hofrichter2, Joerg Schroeder2, Thomas Haaf2, Torsten Rahne3, Rudolf Hagen1, Sebastian P Schraven4. 1. Department of Oto-Rhino-Laryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, Comprehensive Hearing Center, University Hospital Würzburg. 2. Institute of Human Genetics, University of Würzburg, Biozentrum, Würzburg, Germany. 3. Department of Otorhinolaryngology, Head and Neck Surgery, University of Halle-Wittenberg, Halle (Saale). 4. Department of Oto-Rhino-Laryngology, Head and Neck Surgery "Otto Körner", University Hospital Rostock, Rostock, Germany.
Abstract
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.
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.
Authors: Zdeněk Čada; Dana Šafka Brožková; Zuzana Balatková; Pavlína Plevová; Dagmar Rašková; Jana Laštůvková; Rudolf Černý; Veronika Bandúrová; Vladimír Koucký; Silvie Hrubá; Martin Komarc; Ján Jenčík; Simona Poisson Marková; Jan Plzák; Jan Kluh; Pavel Seeman Journal: Eur Arch Otorhinolaryngol Date: 2019-09-24 Impact factor: 2.503