To investigate the hearing loss status and prevalence of mutations in genes associated with deafness in deafness patients from Shandong, to identify pathogenic causes of hearing impairment.

Our study included a total of 5 664 hearing-impaired patients with a hearing disability certificate or a diagnosis of hearing loss, who participated in the genetic testing program for hereditary hearing loss in Shandong Province from 2016 to 2020. Hearing loss was tested by pure-tone audiometry. Genetic testing was carried out with DNA microarray to detect mutations at 15 loci in four common hereditary deafness-related genes.

Among the 5 664 cases, 3 891 had grade 1 (mild) hearing disability, 1 463 had grade 2 (moderate) hearing disability, 188 had grade 3 (severe) hearing disability, 73 had grade 4 (profound) hearing disability, and the remaining 49 consisting of 38 cases of microtia and 11 cases of external auditory canal closure. In terms of deafness-related gene mutations, 2 503 cases were detected with mutations, 1 227 of them (21.66%) carrying GJB2 gene mutations, 975 (17.21%) carrying SLC26A4 gene mutations, 97 (1.71%) carrying mitochondrial 12S rRNA gene mutations, 158 (2.79%) carrying GJB3 gene mutations, and 46 (0.81%) carrying double heterozygous mutations. Both GJB2 and SLC26A4 gene mutations were hotspot mutations in patients with grades 1-4 hearing disability. The prevalence of mutations in GJB2 and SLC26A4 genes was higher in those with grade 1 hearing disability than in those with grade 2 hearing disability (P<0.05) .

Of four common genes related to hereditary deafness, mutations in GJB2 and SLC26A4 genes have been found to be major hotspot mutations in these participants from Shandong. Further research needs to be carried out in many unknown areas for deafness-related genes. Besides, marriage and childbirth guidance for individuals of different genotypes could reduce the vertical transmission of deafness in deaf-to-deaf marriages and subsequently control the birth of new hearing-impaired children in the region.

了解山东省听力障碍患者听力损失情况和失聪基因突变频率，明确听力障碍致病原因。

对2016—2020年参加山东省听力障碍人士失聪基因检测项目的5 664例持听力残疾证或持听力诊断证明的听力障碍患者进行遗传性失聪基因筛查检测，通过纯音测听检测听力障碍患者听力损失情况，应用常见的4个基因15位点遗传性失聪基因芯片进行基因检测。

5 664例听力障碍患者中，听力残疾一级3 891例，听力残疾二级1 463例，听力残疾三级188例，听力残疾四级73例，其余49例（小耳畸形38例，外耳道封闭11例）。5 664例听力障碍患者检测出失聪基因突变者2 503例，其中GJB2基因突变1 227例（携带率为21.66%），SLC26A4基因突变975例（携带率为17.21%），线粒体12SrRNA基因突变97例（携带率为1.71%）；GJB3基因突变158例（携带率为2.79%）；双基因杂合突变46例（携带率为0.81%）。GJB2、SLC26A4基因突变在听力等级中比较一致，属于热点突变。携带GJB2基因、SLC26A4基因突变患者听力一级比例高于听力二级（P<0.05）。

山东省听力障碍患者中常见的4个遗传性失聪基因热点突变主要集中在GJB2基因和SLC26A4基因上；失聪相关基因尚存有许多未知的领域，有待于进一步研究。通过对不同基因型个体进行婚育指导，可以降低聋-聋婚配中聋病的垂直传递，减少本地区新生听力障碍儿童的出生。