Li Weimin, Han Dongyi, Yuan Huijun, Cao Juyang
Department of Otolaryngology-Head and Neck Surgery, Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, 100853, China.
Lin Chuang Er Bi Yan Hou Ke Za Zhi. 2004 Oct;18(10):582-5, 589.
To investigate the proportion of mtDNA mutation in the non-syndromic genetic hearing loss (NSHL) pedigrees and the genetics statistical formulae for maternal inheritance, to study the relationship of mtDNA mutation and inherited deafness, to identify the incidence of the mtDNA mutation in such pedigrees and sporadic patients with Sensorineural hearing loss (SNHL).
Twenty-nine pedigrees with NSHL were collected. Pedigree Investigation was taken. Modal Genetics Analysis. Segregation Analysis were taken. Blood samples were obtained from these pedigrees. DNA was extracted from the isolated leukocytes. The mtDNA 1555G, 7445G, 3243G mutation were examined by multiplex PCR. The sequence of 12SrRNA, tRNA(Leu(UUR)) and tRNA(Ser(UCN)) gene were examined.
There are 12 pedigrees with mtDNA mutation (i.e. 10 with 1555G and 2 with 7445G) examing by multiplex PCR. Modal Genetics Analysis showed that in irregular dominate genetic pedigrees, the incidence of mtDNA mutation is higher than that of regular dominate pedigrees. Segregation Analysis with Screening for mtDNA mutation showed that maternal inherited pedigrees did not have the segregate ratio that the autosomal inheritance had. Sequence analysis confirmed that the 12 pedigrees carried mtDNA mutation, among them 10 pedigrees with 1555G mutation, 2 pedigrees with 7445G mutation, no pedigrees with 3243G.
Maternal inherited pedigrees do not have the segregate ratio of the autosomal inheritance, mtDNA mutation have high incidence in NSHL, mostly are 1555G and 7445G mutation. Screening for mtDNA 7445G mutation combined with 1555G examination is of value to clinical use. Multiplex PCR can diagnose mtDNA multi-mutation quickly and facilely.
探讨非综合征型遗传性听力损失（NSHL）家系中线粒体DNA（mtDNA）突变比例及母系遗传的遗传学统计公式，研究mtDNA突变与遗传性耳聋的关系，明确此类家系及散发性感音神经性听力损失（SNHL）患者中mtDNA突变的发生率。
收集29个NSHL家系，进行家系调查、遗传方式分析、分离分析。采集这些家系的血液样本，从分离的白细胞中提取DNA。采用多重聚合酶链反应（PCR）检测mtDNA的1555G、7445G、3243G突变，检测12SrRNA、tRNA（Leu（UUR））和tRNA（Ser（UCN））基因序列。
通过多重PCR检测，有12个家系存在mtDNA突变（即10个家系为1555G突变，2个家系为7445G突变）。遗传方式分析显示，在不规则显性遗传家系中，mtDNA突变发生率高于规则显性家系。对mtDNA突变进行筛选的分离分析表明，母系遗传家系不存在常染色体遗传的分离比例。序列分析证实这12个家系携带mtDNA突变，其中10个家系为第1555位点G突变，2个家系为第7445位点G突变，无家系为第3243位点G突变。
母系遗传家系不存在常染色体遗传的分离比例，mtDNA突变在NSHL中发生率较高，主要为1555G和7445G突变。联合检测mtDNA的7445G突变和1555G突变对临床应用有价值。多重PCR可快速、简便地诊断mtDNA多突变。
