大前庭水管（EVA）是明确的常染色体隐性遗传疾病。在中国，SLC26A4基因缺陷是EVA的主要致病因素。最近研究发现FOXI1和KCNJ10基因突变也参与EVA的发病。然而,10%的中国EVA患者经上述基因检测后仍无法明确分子病因。内耳发育过程中环境因素变异造成的SLC26A4基因转录或转录后异常是这部分患者可能的病因。本课题组前期研究发现，EVA胎儿与正常胎儿内耳的miRNA表达谱存在显著差异。本研究拟以miRNA为切入点，通过全基因组miRNA表达谱芯片、miRNA功能分析、RNAi等技术，研究miRNA在该病发生中的作用，分析表达差异最显著的miRNA调控EVA的信号通路，拟从表观遗传学角度完善EVA的致聋机制理论。针对新发现的EVA致病因子在患者群中进行验证，指导EVA致聋的基因诊断及产前诊断。同时，为大前庭水管相关内耳畸形的基因治疗提供潜在靶标，初步探索该病的基因治疗方式。

Enlarged Vestibular Aqueduct Syndrome(EVAS) is an autosomal recessive interited disease. The defect in SLC26A4 gene is a main factor of EVAS in China. Recent studies suggested that FOXI1 and KCNJ10 gene also involved in the pathogenesis of EVAS. However, clear molcular etiology can't be determined after testing for above genes in about 10% of Chinese EVAS patient. Abnormal transcription or post-transcriptional process caused by environmental factor might be the causative reason in these patients. Our preliminary data found significant difference of miRNA expressional pattern between normal and EVAS fetus. This study will use the techniques of whole genome miRNA expressional chips, miRNA functional assay, RNAi to study the role of miRNA in the pathogenesis of EVAS. The signal pathway of miRNA regulation in EVAS will be analyzed and the pathogenesis of this disease will be discussed by epigenetic view. The possible new causative factors will be validated in EVAS population, which will provide useful information in genetic testing and prenatal testing. Meanwhile, this study might provide potential targets of gene therapy for patients with EVAS.