Department of Otolaryngology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Province Key Laboratory of Otolaryngology Critical Diseases, Changsha, Hunan, China.
PLoS One. 2019 Apr 11;14(4):e0215212. doi: 10.1371/journal.pone.0215212. eCollection 2019.
Hearing loss (HL) is a common sensory disorder. More than half of HL cases can be attributed to genetic causes. There is no effective therapy for genetic HL at present, early diagnosis to reduce the incidence of genetic HL is important for clinical intervention in genetic HL. Previous studies have identified 111 nonsyndromic hearing loss genes. The most frequently mutated genes identified in NSHL patients in China include GJB2, SLC26A4, and the mitochondrial gene MT-RNR1. It is important to develop HL gene panels in Chinese population, which allow for etiologic diagnosis of both SHL and NSHL. In this study, a total of 220 unrelated Han Chinese patients with bilateral progressive SNHL and 50 unrelated healthy controls were performed Single nucleotide polymorphism (SNP) genotyping using an improved multiplex ligation detection reaction (iMLDR) technique, is to simultaneously detect a total of 32 mutations in ten HL genes, covering all currently characterized mutations involved in the etiology of nonsyndromic or syndromic hearing loss in the Chinese population. The 49 positive samples with known mutations were successfully detected using the iMLDR Technique. For 171 SNHL patients, gene variants were found in 57 cases (33.33%), among which, 30 patients carried mutations in GJB2, 14 patients carried mutations in SLC26A4, seven patients carried mutations in GJB3, and six patients carried mutations in MT-RNR1. The molecular etiology of deafness was confirmed in 12.9% (22/171) of patients carried homozygous variants. These results were verified by Sanger sequencing, indicating that the sensitivity and specificity of the iMLDR technique was 100%. We believe that the implementation of this population-specific technology at an efficient clinical level would have great value in HL diagnosis and treatment.
听力损失（HL）是一种常见的感觉障碍。超过一半的 HL 病例可归因于遗传原因。目前，对于遗传性 HL 尚无有效的治疗方法，早期诊断遗传性 HL 对于遗传性 HL 的临床干预很重要。以前的研究已经确定了 111 个非综合征性听力损失基因。在中国 NSHL 患者中最常突变的基因包括 GJB2、SLC26A4 和线粒体基因 MT-RNR1。在中国人群中开发 HL 基因谱对于 SHL 和 NSHL 的病因诊断非常重要。在这项研究中，使用改良多重连接检测反应（iMLDR）技术对 220 名无关汉族双侧进行性 SNHL 患者和 50 名无关健康对照进行了单核苷酸多态性（SNP）基因分型，该技术可以同时检测十个 HL 基因中的总共 32 个突变，涵盖了中国人群中所有与非综合征性或综合征性听力损失病因相关的目前已描述的突变。使用 iMLDR 技术成功检测到 49 个具有已知突变的阳性样本。对于 171 名 SNHL 患者，在 57 例（33.33%）中发现了基因变异，其中 30 例患者携带 GJB2 突变，14 例患者携带 SLC26A4 突变，7 例患者携带 GJB3 突变，6 例患者携带 MT-RNR1 突变。12.9%（22/171）的纯合变异患者的耳聋分子病因得到了证实。这些结果通过 Sanger 测序得到了验证，表明 iMLDR 技术的灵敏度和特异性为 100%。我们相信，在高效的临床水平上实施这种特定于人群的技术，对于 HL 的诊断和治疗将具有巨大的价值。
