Page 106 - 中国全科医学2022-05

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Results of Hearing Test Combined with Gene Test for Deafness in Patients with Hearing Impairment：an Analysis of
5 664 Cases from Shandong Province SUN Yi，PAN Chiguo，SUN Lili，LI Meng，ZHANG Di，ZHANG Kaiqi，LI Chao *
Shandong Rehabilitation Research Center /Shandong Rehabilitation Hospital，Ji'nan 250109，China
*
Corresponding author：LI Chao，Associate chief physician；E-mail：3291886966@qq.com
【Abstract】 Background As a common disease causing human health impairment and disability，deafness has a
leading morbidity among all the disabling diseases. Many factors could lead to deafness，among which genetic factors account
for about 60%. Gene screening and pedigree analysis can be used to determine whether one has hereditary deafness，so as to
provide corresponding genetic counseling services for hereditary deafness patients to stop the transmission of deafness from
one generation to the next. Objective 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. Methods 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. Results 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）.
Conclusion 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.
【Key words】 Hearing disorders；Deafness；Genetic testing；Hearing tests；Genetic counseling

失聪——人和人之间一道无声的墙，是困扰生活最常见 本研究发现及改进：
的疾病之一。我国失聪患者超过 3 000 万 ［1］ ，其中遗传因素 通过针对听力障碍患者进行遗传性失聪基因检测，
占 60% 以上 ［2-3］ 。近些年，基因检测技术的发展对遗传性失
发现在山东地区 GJB2 基因 235delC 位点和 SLC26A4 基因
聪分子病因的阐明起了巨大推动作用，使早诊断、早发现成
IVS7-2A>G 位点是遗传性失聪基因发病率最高的突变位点；
为现实，通过对听力障碍患者进行基因检测、分析病因，可
按本研究所采用的 4 个常见致聋基因的 15 个热点突变位点
预估下一代患病风险。但不断改进的分子诊断技术一方面可
的微阵列芯片的检测方法相对落后，不能提供准确的临床
提高检出率，另一方面也面临着新检测技术带来的数据分析
基因诊断；因此，后续研究中应系统进行失聪相关基因的
困难和变异解读的不确定性等问题。因此在听力障碍患者中
全序列分析，为本地区失聪基因突变图谱的绘制提供依据。
开展能明确病因的基因检测和遗传咨询十分必要。研究表明
我国失聪患者致病热点基因有 4 个 ［4-5］ 。本研究利用基因芯 下证件者 1 183 例，余 52 例持多重残疾证件。样本采集前相
片技术对山东省听力障碍患者进行 4 种常见致聋基因的 15 个 关专业医护人员向研究对象简单介绍听力检测及失聪基因检
突变位点基因检测，进一步了解山东地区失聪患者基因突变 测，并指导其填写《检测人员信息登记表》，包括基本信息、
情况、完善山东省聋病的分子流行学资料，为听力残疾预防 失聪发病年龄、家族史、耳毒性药物应用史、创伤史等，签
提供参考，进而实现防聋减残、提高人口素质的目的。 署知情同意书。本研究通过本院医学伦理委员会同意〔伦理
1 对象与方法 审批编号：2021-（3）〕。
1.1 研究对象 对 2016—2020 年参加山东省听力障碍人士失 1.2 听力检测 使用纯音测听法检测患者听力，根据我国
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 2006 年第二次全国残疾人抽样调查诊断标准中的 0.5、1、
听力障碍患者进行遗传性失聪基因筛查检测，<18 岁 2 527 例， 2、4 kHz 的听阈均值进行计算。听力残疾一级，平均听阈
18~30 岁 2 036 例，>30 岁 1 101 例；男 2 106 例，女 3 558 例； ≥ 91 dB HL；听力残疾二级，平均听阈 81~90 dB HL；听力
持听力残疾二级及以上证件者 4 429 例，持听力残疾三级及以 残疾三级，平均听阈 61~80 dB HL；听力残疾四级，平均听阈