V-ATP酶相关基因突变导致遗传性耳聋研究进展

Research Progress on Hereditary Deafness Caused by Mutations of V-ATPase Related Genes

V-ATP酶通过水解ATP获得的能量,介导逆电化学梯度跨膜泵H+,在溶酶体酸化和细胞骨架的形成与稳定中发挥重要作用。60%以上的先天性耳聋由遗传因素引起,超过50%的先天性感音神经性耳聋为遗传性耳聋。过去的新生儿耳聋筛查基因主要为GJB2、GJB3、SLC26A4和12SrRNA等;近年来,越来越多的V-ATP酶相关基因突变所致感音神经性耳聋病例被报道,这为新生儿听力筛查提供新的靶点。当前已报道的耳聋相关VATP酶基因主要为ATP6V1B2、ATP6V1B1和ATP6V0A4,其致聋机制与溶酶体酸化异常有关。本文就这三个基因有关耳聋的主要突变,突变所引起的主要临床症状,以及分子病理学机制研究展开综述,有望为临床诊断和机制研究提供参考。

V-ATPase mediates the reverse electrochemical gradient transmembrane pump H+,which plays an important role in lysosomal acidification and cytoskeleton formation and stabilization through the energy obtained by hydrolyzing ATP.More than 60%of cases of congenital deafness are caused by genetic factors,and more than 50%of congenital sensorineural deafness is hereditary deafness.In the past,the main genes screened for congenital deafness were GJB2,GJB3,SLC26A4 and 12SrRNA.In recent years,more and more cases of sensorineural deafness caused by VATPase related gene mutations have been reported,which provides a new target for neonatal screening.ATP6V1B2,ATP6V1B1 and ATP6V0A4 have been reported to be the main V-ATPase genes related to deafness,and the mechanism is related to lysosomal acidification.In this paper,main mutations of these three genes related to deafness,clinical presentations caused by the mutations,and molecular pathological mechanisms are reviewed,to hopefully provide a basis for clinical diagnosis and mechanism research.