慢性进行性外眼肌麻痹(CPEO)是最常见的线粒体疾病之一。它的特点是双边的,眼外肌活动性的缓慢丧失,眼轮匝肌无力,上睑下垂,和其他神经肌肉症状,这是由多个线粒体DNA(mtDNA)缺失的积累引起的。不同核基因的许多突变,如POLG1、POLG2、ANT1等,已被描述为导致常染色体遗传性CPEO并伴有多个mtDNA缺失。大多数致病基因与mtDNA复制损伤有关。这里,我们报告了一个以多个肌肉mtDNA缺失为特征的CPEO样症状的家庭,上睑下垂,糖尿病,听力损失,智力迟钝,和情绪不稳定。我们进行了遗传分析以鉴定家族中的核基因突变。通过全外显子组测序分析来自先证者的DNA。除了可能的致病突变,罕见变异体优先用于基因功能表型解释.我们在PRIMPOL中发现了可能的致病突变,BRCA1、CPT2和GJB2基因,以及CARD8和MEFV基因的功能多态性。多种功能多态性和可能的致病突变可能以复合方式导致线粒体疾病样表型。
Chronic progressive external ophthalmoplegia (CPEO) is one of the most common mitochondrial disorders. It is characterized by bilateral, slowly progressing loss of extraocular muscle mobility, orbicularis oculi weakness, ptosis, and other neuromuscular symptoms, which are caused by the accumulation of multiple mitochondrial DNA (mtDNA) deletions. Many mutations in different nuclear genes, such as POLG1, POLG2, ANT1, and others, have been described as causing autosomal-inherited CPEO with multiple mtDNA deletions. Most causative genes are involved in mtDNA replication impairment. Here, we report a family with CPEO-like symptoms characterized by multiple muscle mtDNA deletions, ptosis, diabetes, hearing loss, mental retardation, and emotional instability. We performed genetic analyses to identify nuclear gene mutations in the family. DNA from the proband was analyzed by whole-exome sequencing. In addition to possible pathogenic mutations, rare variants were prioritized for gene-functional phenotype interpretation. We found possible pathogenetic mutations in the PRIMPOL, BRCA1, CPT2, and GJB2 genes, and functional polymorphisms in the CARD8, and MEFV genes. Multiple functional polymorphisms and possible pathogenic mutations may contribute to mitochondrial-disease-like phenotypes in a composite manner.