Maternally inherited aminoglycoside-induced and nonsyndromic hearing loss is associated with the 12S rRNA C1494T mutation in three Han Chinese pedigrees
Maternally inherited aminoglycoside-induced and nonsyndromic hearing loss is associated with the 12S rRNA C1494T mutation in three Han Chinese pedigrees
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DOI：
10.1016/j.gene.2007.06.009
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发表时间：
2007-10-15
期刊：
影响因子：
3.5
通讯作者：
Guan, Min-Xin
中科院分区：
文献类型：
--
作者：
Chen, Jianfu;Yang, Li;Guan, Min-Xin
我们在这里报告临床。三个患有母系传播的氨基糖苷类诱导性和非综合征性双侧听力损失的汉族谱系的遗传和分子特征。临床评估显示，在这些家庭中的母系亲属的听力障碍的严重程度，发病年龄和听力配置的范围很广。这些家系中听力损失的发生率分别为28%、20%和15%，平均为21%。排除氨基糖甙类药物的影响后，7个家系的听力损失发生率分别为21%、13%和8%，平均为14%。在这些家系中的完整线粒体基因组的序列分析表明，除了属于东亚单倍型群F1a1，F1a1和D5a2，分别不同的mtDNA多态性的存在下，与遗传相关的12S rRNA C1494T突变。这表明C1494T突变是偶发性的，并通过mtDNA的进化而增殖。tRNA和rRNA的功能突变或继发性LHON突变的缺失提示这些mtDNA单倍型群特异性变异可能在这些中国家系中C1494T突变的表型表达中不起重要作用。此外，GJB 2基因缺乏显着突变排除了GJB 2可能参与受影响受试者C1494 T突变的表型表达。然而，氨基糖苷类和其他核修饰基因在这些中国家庭的C1494T突变的表型表现中起修饰作用。(c)2007 Elsevier B.V保留所有权利。
We report here the clinical. genetic and molecular characterization of three Han Chinese pedigrees with maternally transmitted aminoglycoside-induced and nonsyndromic bilateral hearing loss. Clinical evaluation revealed the wide range of severity, age-at-onset and audiometric configuration of hearing impairment in matrilineal relatives in these families. The penetrances of hearing loss in these pedigrees were 28%, 20%, and 15%, with an average of 21%, when arninoglycoside-induced deafness was included. When the effect of aminoglycosides was excluded, the penetrances of hearing loss in these seven pedigrees were 21%, 13% and 8%, with an average of 14%. Sequence analysis of the complete mitochondrial genomes in these pedigrees showed the presence of the deafness-associated 12S rRNA C1494T mutation, in addition to distinct sets of mtDNA polymorphism belonging to Eastern Asian haplogroups F1a1, F1a1 and D5a2, respectively. This suggested that the C 1494T mutation occurred sporadically and multiplied through evolution of the mtDNA. The absence of functionally significant mutations in tRNA and rRNAs or secondary LHON mutations in their mtDNA suggests that these mtDNA haplogroup-specific variants may not play an important role in the phenotypic expression of the C1494T mutation in those Chinese families. In addition, the lack of significant mutation in the GJB2 gene ruled out the possible involvement of GJB2 in the phenotypic expression of the C1494T mutation in those affected subjects. However, aminoglycosides and other nuclear modifier genes play a modifying role in the phenotypic manifestation of the C1494T mutation in these Chinese families. (c) 2007 Elsevier B.V All rights reserved.