Faculty of Medicine and Health Sciences, Ghent University, Corneel Heymanslaan 10, B-9000 Ghent, Belgium.
Department of Otorhinolaryngology, Ghent University Hospital, Corneel Heymanslaan 10, B-9000 Ghent, Belgium.
Genes (Basel). 2022 Dec 29;14(1):105. doi: 10.3390/genes14010105.
Congenital hearing loss has an impact on almost every facet of life. In more than 50% of cases, a genetic cause can be identified. Currently, extensive genetic testing is available, although the etiology of some patients with obvious familial hearing loss remains unknown. We selected a cohort of mutation-negative patients to optimize the diagnostic yield for genetic hearing impairment. In this retrospective study, 21 patients (17 families) with negative molecular diagnostics for non-syndromic hearing loss (gene panel analysis) were included based on a positive family history with a similar type of hearing loss. Additional genetic testing was performed using a whole exome sequencing panel (WESHL panel v2.0) in four families with the strongest likelihood of genetic hearing impairment. In this cohort ( = 21), the severity of hearing loss was most commonly moderate (52%). Additional genetic testing revealed pathogenic copy number variants in the gene in two families. In summary, regular re-evaluation of hearing loss patients with presumably genetic etiology after negative molecular diagnostics is recommended, as we might miss newly discovered deafness genes. The switch from gene panel analysis to whole exome sequencing or whole genome sequencing for the testing of congenital hearing loss seems promising.
先天性听力损失几乎会对生活的各个方面产生影响。在超过 50%的病例中，可以确定遗传原因。目前，有广泛的基因检测可用，尽管一些有明显家族性听力损失的患者的病因仍然未知。我们选择了一组突变阴性患者，以优化遗传性听力障碍的诊断效果。在这项回顾性研究中，根据具有相似类型听力损失的阳性家族史，我们纳入了 21 名（17 个家庭）非综合征性听力损失（基因panel 分析）分子诊断阴性的患者。在最有可能存在遗传性听力障碍的 4 个家庭中，使用全外显子组测序panel（WESHL panel v2.0）进行了额外的基因检测。在该队列（=21）中，听力损失的严重程度最常见为中度（52%）。额外的基因检测显示，两个家庭的 基因存在致病性拷贝数变异。总之，建议对分子诊断阴性的疑似遗传性病因的听力损失患者定期重新评估，因为我们可能会错过新发现的耳聋基因。从基因panel 分析切换到全外显子组测序或全基因组测序来检测先天性听力损失似乎很有前景。
