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目的 :探讨非综合征型遗传性聋 (NSHL)家系中线粒体基因 (mtDNA)突变所占比重以及母系遗传的统计学规律。探讨mtDNA突变与遗传性聋的关系及突变在这类家系及散发感音神经性聋 (SNHL)中的发生率。方法 :收集遗传性NSHL家系 2 9个 ,行家系调查 ;对家系进行形式遗传学分析、分离分析 ;采取外周血 ,从白细胞中抽取DNA ;以多重聚合酶链反应 (PCR)法检测mtDNA (nt) 15 5 5 G、74 4 5 G、32 4 3G 点突变 ;行mtDNA12SrRNA ,tRNALeu(UUR) 及tRNASer(UCN) 基因序列测定。结果 :多重PCR检测示mtDNA突变家系 12个 ;形式遗传学分析确定为显性遗传不规则外显的家系 ,mtDNA突变率高 ;分离分析结合mtDNA突变检测示 :母系遗传不具有常染色体遗传基因分离比。经测序证实 ,12个家系具有mtDNA突变 ;形式为 :15 5 5 G 突变家系 10个 ,74 4 5 G突变家系 2个 ,未发现 32 4 3G 突变家系。结论 :母系遗传与常染色体显性及隐性遗传基因传递分离比有差异 ;mtDNA突变在NSHL中占较高比例 ,主要形式是 15 5 5 G 及 74 4 5 G 突变。在散发病例中发生率很低 ;74 4 5 G结合15 5 5 G 点突变筛查对SNHL的诊断有重要意义。多重PCR法是mtDNA多基因突变位点简便的检测方法
Objective: To investigate the proportion of mitochondrial DNA (mtDNA) mutations in non-syndromic hereditary deafness (NSHL) pedigrees and the statistical rules of maternal inheritance. To investigate the relationship between mtDNA mutations and hereditary deafness and the incidence of mutations in these families and sporadic sensorineural hearing loss (SNHL). Methods: Totally 29 hereditary NSHL pedigrees were investigated. The pedigree was investigated by genetic typing and analyzed by genetic analysis. Peripheral blood was collected and DNA was extracted from white blood cells. Multiplex PCR was used to detect mtDNA ) 15 5 5 G, 74 4 5 G, 32 4 3G point mutations; and sequencing of mtDNA12SrRNA, tRNALeu (UUR) and tRNASer (UCN) genes. RESULTS: Twelve mtDNA mutants were detected by multiplex PCR. The mtDNA mutation rate was high in the genotypes with dominant genetic irregularities. The segregation analysis combined with the mtDNA mutation showed that the maternal inheritance did not have autosomal genetic segregation ratio. Sequencing confirmed that 12 of the 12 families had mtDNA mutations; 10 were 15 5 5 G mutants and 2 74 4 5 G mutants, and no 32 4 3G mutant pedigrees were found. CONCLUSION: There are differences in maternal inheritance and autosomal dominant and recessive genetic transmission. The mtDNA mutations account for a high proportion of NSHL, the main forms are 15 5 5 G and 74 4 5 G mutations. The incidence of sporadic cases is very low; 74 4 5 G combined with 15 5 5 G point mutation screening of SNHL diagnosis of great significance. Multiplex PCR method is a simple and convenient method for detecting mtDNA multiple gene mutation sites