Phenotype characterization of 9 patients with mutations in DFNB16-gene

Introduction:

Hearing loss belongs to the most frequent congenital diseases; 50 – 70% of cases with congenital hearing loss are caused by genetic defects. DFNB1 (Connexin26) is the most frequently affected gene in 20 – 40% in these patients. Despite the great genetic heterogeneity of hearing loss, detection of rare genes such as DFNB16 (Stereocilin) is possible. The genetic architecture of the DFNB16 locus is challenging and requires a unique Sanger sequencing assay. The aim of the study is a systemic analysis of the audiological data of DFNB16-positive patients to characterize the phenotype.

Methods:

Since 2011, 290 patients with suspicion of inherited hearing loss received a human genetic exploration. 141 patients with negative DFNB1 results received further testing in the DFNB16 locus. All patients obtained complete audiological diagnostic workup. Additionally epidemiological data like age, newborn-hearing-screening result and type of hearing aid were analysed.

Results:

9 of 141 (6%) of the examined patients (mean age 5 years; range: 0 – 13 years) showed mutations in the DFNB16-gene (6 compound heterozygous, 6 homozygous). Beside a moderate hearing loss in the pure tone audiogram, ABR thresholds were at 40 – 50 dB nHL. Otoacoustic emissions (TEOAE) were detectable in only one patient. All patients were fitted with hearing aids.

Conclusions:

Examination of the DFNB16-locus should be a standard diagnostic test when DFNB1-gene screening is negative. DFNB16-associated hearing loss can be audiologically characterised as moderate sensorineural hearing loss in the main speech field with absent otoacoustic emissions.

Publication History

Publication Date:
18 April 2018 (online)