Zhang Ting, Chen Bo-bei, Zheng Jing, Gong Sha-sha, Zhang Chu-qin, Lv Jian-xin, Guan Min-xin
Attardi Institute of Mitochondrial Biomedicine and Zhejiang Provincial Key Laboratory of Medical Genetics, Wenzhou Medical College, Wenzhou, Zhejiang 325035, P. R. China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2011 Aug;28(4):367-73. doi: 10.3760/cma.j.issn.1003-9406.2011.04.002.
To study the effect of the mitochondrial 12S rRNA mutations on aminoglycoside-induced and nonsyndromic hearing loss, to carry out the clinical and molecular characterization of five Han Chinese pedigrees with maternally transmitted aminoglycoside-induced and nonsyndromic hearing loss.
Five pedigrees of maternally transmitted aminoglycoside-induced and nonsyndromic hearing loss were collected, genomic DNA was extracted, and complete mitochondrial genomes and the gap junction protein beta 2 (GJB2) gene were amplified and sequenced.
Clinical evaluation revealed a wide range of severity, age-at-onset and audiometric configuration of hearing impairment in the matrilineal relatives in these families. The penetrance rates of hearing loss in these pedigrees were 17.6%, 50.0%, 66.7%, 31.3% and 23.1%, with an average of 37.7%, when aminoglycoside-induced deafness was included. Sequence analysis of the complete mitochondrial genomes in these pedigrees identified the known 1555A>G mutation and distinct sets of mitochondrial DNA(mtDNA) polymorphisms belonging to Eastern Asian haplogroups D4b2b, B4c1b1, F3, C1 and D5a, respectively. Of these variants, ND1 L89T and CO3 A200T mutations resided at the highly conservative regions. However, there were no functionally significant mutations in tRNAs and rRNAs or secondary known mutations. No hearing loss related GJB2 gene mutation was observed.
The lack of significant mutation in the ruled out the possible involvement of GJB2 in the phenotypic expression of the 1555A>G mutation in those affected subjects. However, aminoglycosides, mtDNA variations and other nuclear modifier genes may play an important role in the phenotypic manifestation of the 1555A>G mutation in these Chinese families.
研究线粒体12S rRNA突变对氨基糖苷类药物所致及非综合征性听力损失的影响，对5个母系遗传的氨基糖苷类药物所致及非综合征性听力损失的汉族家系进行临床和分子特征分析。
收集5个母系遗传的氨基糖苷类药物所致及非综合征性听力损失家系，提取基因组DNA，扩增并测序完整的线粒体基因组和缝隙连接蛋白β2（GJB2）基因。
临床评估显示，这些家族中母系亲属的听力障碍严重程度、发病年龄和听力图类型差异很大。当纳入氨基糖苷类药物所致耳聋时，这些家系中听力损失的外显率分别为17.6%、50.0%、66.7%、31.3%和23.1%，平均为37.7%。对这些家系的完整线粒体基因组进行序列分析，鉴定出已知的1555A>G突变以及分别属于东亚单倍群D4b2b、B4c1b1、F3、C1和D5a的不同线粒体DNA（mtDNA）多态性集合。在这些变异中，ND1 L89T和CO3 A200T突变位于高度保守区域。然而，tRNA和rRNA中没有功能上显著的突变或已知的继发突变。未观察到与听力损失相关的GJB2基因突变。
排除了GJB2在这些受影响受试者1555A>G突变表型表达中的可能参与。然而，氨基糖苷类药物、mtDNA变异和其他核修饰基因可能在这些中国家系1555A>G突变的表型表现中起重要作用。
