遗传性听神经病一家系线粒体DNA全序列分析

目的 通过对一个遗传性听神经病家系进行线粒体DNA全序列分析，为确定其遗传方式提供分子基础。方法 选择一个4代11人的听神经病核心家系为研究对象，对现存9名成员及40例散发聋患者外周血DNA进行12 S rRNA（nt1095）聚合酶链反应（PCR）扩增，以及对一例患者进行线粒体DNA全序列PCR扩增。扩增产物通过基因测序进行突变检测和分析。结果 所有研究对象的基因区域均扩增成功。9名家系成员及40例散发聋个体12 S rRNA（nt1095）突变检测均为阴性。对一例患者线粒体DNA全序列分析发现了一系列单核苷酸多态性位点，以及一个位于MT-C01区的nt6251T→C转换，后者为一同义突变。结论该家系成员不存在线粒体DNA 12 S rRNA T1095C突变，对线粒体DNA全序列分析也未发现有意义的突变位点。结合临床特征和家系谱患者传递规律，确定该家系遗传方式为常染色体显性遗传。

Whole mitochondrial DNA analysis of one auditory neuropathy family

Objective By screening the whole sequence of mitochondrial DNA (mtDNA) of an auditory neuropathy (AN) family, to confirm the hereditary pattern of this AN family on molecular basis. Methods A kernel pedigree with auditory neuropathy was selected for this study. PCR amplifications aiming at mtDNA 12 S rRNA (nt1095) was conducted in nine family members and 40 sporadic deaf patients, and the whole mtDNA fragments were amplified using PCR in one of the AN patients. PCR products were sequenced to identify the mutations. Results PCR amplifications were successfully conducted in all subjects. No 12 S rRNA(nt1095) mutation was detected in either the family members or the sporadic deaf patients. In one family member with auditory neuropathy who was screened the whole mtDNA,a series of single nucleotide polymorphisms and a novel mutation T6251C were detected. The latter was confirmed to be a synonymous mutation locating at MT-CO1 gene. Conclusions There is no mtDNA 12 S rRNA T1095C mutation in this AN family. The whole mtDNA screening has not identified meaningful mutations. Considering the clinical characteristics and the family pedigree,it is concluded that the hearing loss in this AN family is transmitted via autosomal dominant gene.