Masindova I, Varga L, Stanik J, Valentinova L, Profant M, Klimes I, Gasperikova D
Laboratory of Diabetes and Metabolic Disorders & DIABGENE, Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava, Slovakia.
Endocr Regul. 2012 Jul;46(3):167-86. doi: 10.4149/endo_2012_03_167.
Hearing loss is one of the most widespread sensory disorders. The incidence of deafness in general population is 1:1000 newborns. About one half of the cases of the congenital sensorineural hearing loss (SNHL) is inherited. Recessive mutations in the gap junction beta 2 (GJB2) gene are the most common genetic causes of the nonsyndromic SNHL. The GJB2 encodes a protein connexin 26 which forms a subunit of gap junction essential for the correct function of the inner ear. The syndromic SNHL is associated with a wide range of other symptoms, which encompass also dysfunctions of endocrine organs. The Pendred syndrome associated with the hearing impairment is characterized by a prelingual, bilateral sever to profound SNHL, goiter, and iodine organification defect. It is an autosomal recessive disorder, which develops due to mutations in pendrin, an anion channel encoded by SLC26A4 gene. Another important type of syndromic hearing loss is the Maternally Inherited Diabetes and Deafness syndrome, which is caused by several mitochondrial DNA mutations. These mutations are clinically manifested by a hearing impairment with development of the diabetes in the adult age. Hearing impairment occurs during puberty when sensation of high frequency tones is affected following with further progress to profound bilateral sensorineural hearing impairment in the whole frequency range. This review deals with the molecular mechanisms of common genetic causes of the hereditary SNHL along with the selected endocrinopathies emphasizing that the DNA analyses along with the functional studies significantly contribute to the early SNHL diagnosis followed by personalized therapy and genetic counseling.
听力损失是最普遍的感觉障碍之一。普通人群中耳聋的发病率为每1000名新生儿中有1例。先天性感音神经性听力损失（SNHL）病例中约有一半是遗传性的。缝隙连接蛋白β2（GJB2）基因的隐性突变是导致非综合征性SNHL的最常见遗传原因。GJB2编码一种连接蛋白26，它形成内耳正常功能所必需的缝隙连接亚基。综合征性SNHL与一系列其他症状相关，其中也包括内分泌器官功能障碍。与听力障碍相关的 Pendred 综合征的特征是语言前、双侧重度至极重度SNHL、甲状腺肿和碘有机化缺陷。它是一种常染色体隐性疾病，由SLC26A4基因编码的阴离子通道pendrin的突变引起。另一种重要的综合征性听力损失类型是母系遗传糖尿病和耳聋综合征，它由几种线粒体DNA突变引起。这些突变在临床上表现为听力障碍，并在成年期出现糖尿病。听力障碍发生在青春期，此时高频音调的感觉受到影响，随后在整个频率范围内进一步发展为重度双侧感音神经性听力障碍。本综述探讨了遗传性SNHL常见遗传原因的分子机制以及所选的内分泌疾病，强调DNA分析和功能研究对早期SNHL诊断、个性化治疗和遗传咨询有显著贡献。
