Molecular study of patients with auditory neuropathy
Molecular study of patients with auditory neuropathy
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DOI：
10.3892/mmr.2016.5226
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发表时间：
2016-07-01
影响因子：
3.4
通讯作者：
Sartorato, Edi Lucia
中科院分区：
文献类型：
--
作者：
De Carvalho, Guilherme Machado;Ramos, Priscila Zonzini;Sartorato, Edi Lucia
听神经病变是一种听力损失，由内耳毛细胞或听神经突触的参与引起听觉刺激的传导改变。其特征是脑干听觉诱发电位检查中波形的缺失或改变，伴有耳声学和/或耳蜗麦克风问题。目前，与非综合征性听神经病变相关的四个基因位点已被定位：常染色体隐性耳聋-9 [DFNB9；otoferlin （OTOF）基因]和常染色体隐性耳聋-59 [DFNB59；与常染色体隐性遗传相关的PJVK基因；常染色体显性听神经病变基因[AUNA1；透明-3 （DIAPH3）基因；此外，连接蛋白26（间隙连接β 2 （GJB2）基因）的突变也与该疾病有关。OTOF基因突变在听神经病变中起重要作用。在不同来源人群的非综合征性耳聋个体中发现了超过80种致病突变，重点是p.Q829X突变，在西班牙人群中发现了大约3%的耳聋病例。识别导致听神经病变的遗传改变是理解听力损失不同表型的分子基础的挑战之一。因此，本研究旨在研究听神经病变患者中OTOF基因的分子变化，并开发一种用于听神经病变分子诊断的DNA芯片，采用质谱法进行基因分型。对47例听力损失和临床诊断为听神经病变的患者进行遗传改变研究，在3例纯合子患者和其中1例的杂合子父母中发现GJB2基因c.35delG突变。此外，通过对48个外显子的完整测序来追踪OTOF基因突变，尽管这些结果仍处于初步阶段。研究听神经病变的遗传基础对于鉴别诊断、制定更具体的治疗方法和更准确的遗传咨询至关重要。
Auditory neuropathy is a type of hearing loss that constitutes a change in the conduct of the auditory stimulus by the involvement of inner hair cells or auditory nerve synapses. It is characterized by the absence or alteration of waves in the examination of brainstem auditory evoked potentials, with otoacoustic and/or cochlear microphonic issues. At present, four loci associated with non-syndromic auditory neuropathy have been mapped: Autosomal recessive deafness-9 [DFNB9; the otoferlin (OTOF) gene] and autosomal recessive deafness-59 [DFNB59; the pejvakin (PJVK) gene], associated with autosomal recessive inheritance; the autosomal dominant auditory neuropathy gene [AUNA1; the diaphanous-3 (DIAPH3) gene]; and AUNX1, linked to chromosome X. Furthermore, mutations of connexin 26[the gap junction beta 2 (GJB2) gene] have also been associated with the disease. OTOF gene mutations exert a significant role in auditory neuropathy. In excess of 80 pathogenic mutations have been identified in individuals with non-syndromic deafness in populations of different origins, with an emphasis on the p.Q829X mutation, which was found in similar to 3% of cases of deafness in the Spanish population. The identification of genetic alterations responsible for auditory neuropathy is one of the challenges contributing to understand the molecular bases of the different phenotypes of hearing loss. Thus, the present study aimed to investigate molecular changes in the OTOF gene in patients with auditory neuropathy, and to develop a DNA chip for the molecular diagnosis of auditory neuropathy using mass spectrometry for genotyping. Genetic alterations were investigated in 47 patients with hearing loss and clinical diagnosis of auditory neuropathy, and the c.35delG mutation in the GJB2 gene was identified in three homozygous patients, and the heterozygous parents of one of these cases. Additionally, OTOF gene mutations were tracked by complete sequencing of 48 exons, although these results are still preliminary. Studying the genetic basis of auditory neuropathy is of utmost importance for obtaining a differential diagnosis, developing more specific treatments and more accurate genetic counseling.