唐氏综合征患儿线粒体基因组突变的分析

目的 研究唐氏综合征中线粒体DNA突变情况.方法 采用高通量测序和焦磷酸测序检测7个唐氏综合征(Down's syndrome,DS)家系中的患儿和母亲的线粒体基因组序列,分析线粒体基因组序列的变化情况.结果 ①DS患儿中检测到36个与其母亲中不同的线粒体DNA突变,其中14个位点是首次在唐氏综合征样本中发现;②36个线粒体DNA突变主要发生于D-Loop区和线粒体复合物Ⅰ中;③ 线粒体基因组13个编码基因中,有11个基因检测到线粒体DNA的突变;④ 焦磷酸测序对线粒体基因组杂合突变频率的检测结果和高通量测序结果吻合.结论 DS患儿中广泛存在线粒体DNA的突变,这些突变可能与唐氏综合征的线粒体功能异常相关.

Analysis of Mitochondrial Genome Mutation in Children with Down' s Syndrome

Objective To investigate the mitochondrial DNA ( mtDNA) mutations in Down' s Syndrome ( DS) . Methods The mitochondrial genome sequence was detected by high-throughput sequencing and pyrosequencing in child patients and their mothers from seven DS families and the sequence variations were analyzed. Results A total of 36 mitochondrial DNA mutations were detec-ted in children with DS, which were different from the mother mtDNA. Of the 36 mutations, 14 were firstly found in DS patients. These mtDNA mutations occurred mainly in the D-Loop region and complex I. In 13 coding genes of the mitochondrial genome, 11 genes were found to have muta-tions. The heterozygosity frequencies in mitochondrial genome detected by pyrosequencing were in consistent with those analyzed by high-throughput sequencing. Conclusion Mutations in mtDNA are frequently present in children with DS, which may be associated with mitochondrial dysfunction in DS.