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.
Otol Neurotol. 2019 Jan;40(1):e48-e55. doi: 10.1097/MAO.0000000000002059.
We hypothesized that patients with DFNB16 caused hearing loss show characteristical audiological findings depending on genetic results.
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.
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.
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.
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.
我们假设由 DFNB16 引起的听力损失患者根据遗传结果表现出特征性的听力学发现。
听力损失属于最常见的先天性疾病。在 50-70%的个体中，听力损失是由遗传缺陷引起的。DFNB1（感音神经性，常染色体隐性遗传）是最常受影响的基因座。尽管其遗传异质性很大，但对 STRC 等基因的综合分析（编码立体蛋白，DFNB16）是可能的。DFNB16 基因座的遗传结构具有挑战性，需要独特的分子遗传学检测方法。本研究的目的是对 DFNB16 阳性患者的听力学表型进行系统描述。
自 2011 年以来，有 290 名怀疑遗传性听力损失的患者接受了人类遗传探索。82 名 DFNB1 阴性患者进一步在 DFNB16 基因座进行检测。STRc 阳性患者接受了完整的听力学诊断检查。此外，还收集了流行病学数据。
在 82 名接受检查的患者（平均年龄 5 岁）中，有 9 名（11%）患者存在 STRC 突变（3 名纯合子，6 名复合杂合子）。除纯音听力图中中度听力损失外，听觉脑干反应阈值为 40-50dB nHL。仅在一名患者中可检测到耳声发射。
在 DFNB1 基因筛查结果为阴性后，应将 DFNB16 基因座检查作为标准诊断测试。值得注意的是，DFNB16 相关听力损失可在主言语区表现为中度感音神经性听力损失，并伴有耳声发射缺失。本研究首次将听力损失患者的听力学发现与 STRC 的遗传结果相关联。
