Department of Otolaryngology, School of Medicine, University of Colorado Anschutz Medical Campus.
Department of Pediatric Otolaryngology, Children's Hospital Colorado, Colorado.
Otol Neurotol. 2020 Aug;41(7):978-985. doi: 10.1097/MAO.0000000000002671.
To investigate novel variants in hearing loss genes and clinical factors affecting audiometric outcomes of cochlear implant (CI) patients.
Approximately 50% of hearing loss has a genetic etiology, with certain genetic variants more prevalent in specific ethnic groups. Different variants and some clinical variables including inner ear malformations result in different prognoses or clinical outcomes after CI.
Medical and genetic testing records of pediatric CI patients were reviewed for clinical variables. Minor allele frequencies of variants were obtained from Genome Aggregation Database (gnomAD) and variants were classified for pathogenicity. Standard statistical testing was done using Fisher's exact, Wilcoxon, and Spearman correlation tests.
Eighteen CI patients with genetic test results had pathogenic variants, including six patients with syndromic hearing loss and six patients with known GJB2 variants. Novel pathogenic variants were noted in CHD7, ADGRV1, and ARID1B, with variants in the latter two genes identified in Hispanic patients. Overall, carriage of genetic variants was associated with better pre-CI audiometric thresholds at 2000 Hz (p = 0.048). On the other hand, post-CI thresholds were significantly worse in patients with inner ear malformations, particularly in patients with atretic cochlear nerve canals.
Four novel pathogenic variants were identified, which contributes to knowledge of allelic spectrum for hearing loss especially in Hispanic patients. In this cohort, carriage of pathogenic variants particularly of GJB2 variants was associated with better pre-CI audiometric thresholds, while patients with inner ear malformations had worse post-CI audiometric thresholds.
探究听力损失基因中的新型变异以及影响人工耳蜗（CI）患者听力测量结果的临床因素。
约有 50%的听力损失具有遗传病因，某些遗传变异在特定种族群体中更为普遍。不同的变异和一些临床变量，包括内耳畸形，导致 CI 后不同的预后或临床结果。
回顾了儿科 CI 患者的医疗和基因检测记录，以获取临床变量。从基因组聚合数据库（gnomAD）获取变异的次要等位基因频率，并对变异进行致病性分类。使用 Fisher 精确检验、Wilcoxon 检验和 Spearman 相关检验进行标准统计检验。
18 名具有基因检测结果的 CI 患者携带致病性变异，其中包括 6 名综合征性听力损失患者和 6 名已知 GJB2 变异患者。在 CHD7、ADGRV1 和 ARID1B 中发现了新型致病性变异，后两者的基因变异在西班牙裔患者中被发现。总体而言，携带遗传变异与更好的 CI 前 2000Hz 听力阈值相关（p=0.048）。另一方面，内耳畸形患者的 CI 后阈值明显更差，尤其是耳蜗神经管闭锁的患者。
确定了四个新型致病性变异，有助于了解特别是西班牙裔患者的听力损失等位基因谱。在该队列中，携带致病性变异，特别是 GJB2 变异与更好的 CI 前听力阈值相关，而内耳畸形患者的 CI 后听力阈值更差。
