Study of modifiers factors associated to mitochondrial mutations in individuals with hearing impairment
Study of modifiers factors associated to mitochondrial mutations in individuals with hearing impairment
复制标题
DOI：
10.1016/j.bbrc.2009.02.014
复制
发表时间：
2009-04-03
影响因子：
3.1
通讯作者：
Sartorato, Edi Lucia
中科院分区：
文献类型：
--
作者：
Sousa de Moraes, Vanessa Cristine;Alexandrino, Fabiana;Sartorato, Edi Lucia
听力障碍是普通人群中最普遍的感觉障碍。先天性耳聋发生在每 1000 名活产婴儿中，大约有 1 人患有先天性耳聋，其中约 50% 在发展中国家有遗传原因。非综合征性耳聋可由核基因和线粒体基因突变引起。在全球许多家庭中，线粒体 DNA 突变与氨基糖苷类诱发的非综合征性耳聋有关。然而，核背景影响这些致病突变的表型表达。事实上，有人提出核修饰基因调节 MTRNR1 基因中线粒体 A1555G 突变的表型表现。两个假定的核修饰基因 TRMU 和 MTO1 编码与 tRNA 修饰相关的高度保守的线粒体。据推测，人类 TRMU 和 MTO1 核基因可能调节耳聋相关线粒体突变的表型表现。这项工作的目的是阐明线粒体突变、核修饰基因突变和氨基糖苷类暴露对耳聋表型的影响。我们的研究结果表明，个体的遗传背景可能在与线粒体突变和氨基糖苷类诱导的耳聋发病机制中发挥重要作用。 (C) 2009 Elsevier Inc. 保留所有权利。
Hearing impairment is the most prevalent sensorial deficit in the general population. Congenital deafness occurs in about I in 1000 live births, of which approximately 50% has hereditary cause in development countries. Non-syndromic deafness can be caused by mutations in both nuclear and mitochondrial genes. Mutations in mtDNA have been associated with aminoglycoside-induced and non-syndromic deafness in many families worldwide. However, the nuclear background influences the phenotypic expression of these pathogenic Mutations. Indeed, it has been proposed that nuclear modifier genes modulate the phenotypic manifestation of the mitochondrial A1555G mutation in the MTRNR1 gene. The both putative nuclear modifiers genes TRMU and MTO1 encoding a highly conserved mitochondrial related to tRNA modification. It has been hypothesizes that human TRMU and also MTO1 nuclear genes may modulate the phenotypic manifestation of deafness-associated mitochondrial mutations. The aim of this work was to elucidate the contribution of rnitochondrial mutations, nuclear modifier genes Mutations and aminoglycoside exposure in the deafness phenotype. Our findings suggest that the genetic background of individuals may play an important role in the pathogenesis of deafness-associated with mitochondrial mutation and aminoglycoside-induced. (C) 2009 Elsevier Inc. All rights reserved.