Franz Leonardo, Incognito Alessandro, Gallo Chiara, Turolla Licia, Scquizzato Elisa, Cenedese Roberta, Matarazzo Alessandro, Savegnago Daniel, Zanatta Paolo, Genovese Elisabetta, de Filippis Cosimo, Marioni Gino
Phoniatrics and Audiology Unit, Department of Neuroscience DNS, University of Padova, 35122 Treviso, Italy.
Medical Genetics Unit, Treviso Hospital, 31100 Treviso, Italy.
Children (Basel). 2024 Feb 3;11(2):194. doi: 10.3390/children11020194.
GJB2 mutations are the most common cause of autosomal-recessive non-syndromic sensorineural hearing loss (SNHL). The available evidence shows large phenotypic variability across different genotypes and allelic variants. The aim of this study was to investigate the clinical and audiological features of a cohort of subjects with different GJB2/GJB6 gene mutation profiles from a tertiary referral center in Northeastern Italy. We considered 57 patients with GJB2/GJB6 mutations presenting with congenital, non-syndromic SNHL, mainly coming from the Veneto region (Italy). The samples were screened for mutations in exons 1 and 2 of the GJB2 gene and for the GJB6 gene deletion del (GJB6-D13S1830). Free-field and air-conduction frequency-specific thresholds and the pure-tone average (PTA) were considered in the statistical analysis. Five patients (8.87%) had connexin gene mutations in simple heterozygosis, 15 (26.31%) in compound heterozygosis, 34 (59.64%) in homozygosis, and 3 (5.26%) with digenic patterns. The frequency-specific air-conduction thresholds showed significantly different mean values across the different genotypes (Roy's largest-root test, = 0.0473). Despite the evidence already available on genetic SNHL, many new insights are to be expected. Further large-scale prospective studies including different populations are necessary to confirm these preliminary findings about the clinical and audiological features of patients with different GJB2/GJB6 gene mutation patterns.
GJB2基因突变是常染色体隐性非综合征性感音神经性听力损失（SNHL）最常见的病因。现有证据表明，不同基因型和等位基因变异的表型差异很大。本研究的目的是调查来自意大利东北部一家三级转诊中心的一组具有不同GJB2/GJB6基因突变谱的受试者的临床和听力学特征。我们纳入了57例患有GJB2/GJB6突变、表现为先天性非综合征性SNHL的患者，他们主要来自意大利威尼托地区。对样本进行GJB2基因第1和第2外显子的突变筛查以及GJB6基因缺失del（GJB6-D13S1830）的检测。统计分析中考虑了自由声场和空气传导频率特异性阈值以及纯音平均听阈（PTA）。5例患者（8.87%）为单纯杂合子连接蛋白基因突变，15例（26.31%）为复合杂合子，34例（59.64%）为纯合子，3例（5.26%）为双基因模式。不同基因型的频率特异性空气传导阈值显示出显著不同的平均值（Roy最大根检验，P = 0.0473）。尽管已有关于遗传性SNHL的证据，但仍有望获得许多新的见解。有必要开展包括不同人群的进一步大规模前瞻性研究，以证实这些关于不同GJB2/GJB6基因突变模式患者临床和听力学特征的初步发现。
