Clinical Analysis Of Chronic Progressive External Ophthalm Oplegia Related To Nuclear DNA

BackgroundChronic progressive external ophthalmoplegia(CPEO)is a progressive mitochondrial myopathy.The visual difficulties and reduced social identity caused by ocular sequelae cause great pain to patients.Moreover,with the progress of the disease,some patients will have other symptoms of mitochondrial dysfunction.In recent years,with the development of new generation sequencing technology,the genetic basis of mitochondrial myopathy has made new progress,from mitochondrial DNA(mtDNA)deletion and point mutation to nuclear DNA(nDNA)mutation affecting mitochondrial function and replication.However,because mitochondria are controlled by the dual genome of maternal mtDNA and Mendelian nDNA,mitochondrial myopathy has significant heterogeneity,and the relationship between its genotype and clinical phenotype needs to be further studied,ObjectiveTo report the clinical,pathological and genetic features of two patients diagnosed with CPEO related to POLG2 and TWNK gene mutation.Meantime,retrieving the clinical datas of CPEO patients caused by POLG2 and TWNK gene mutations reported at home and abroad,and analyzing the clinical traits,pathological features and genetic features of POLG2 and TWNK,which will help doctors to understand CPEO better.MethodsReviewing the clinical,pathological and genetic characteristics of two CPEO patients taken to the department of neurology of the First Affiliated hospital of Zhengzhou University from June 2017 to March 2019.At the same time,the databases with relatively complete information at home and abroad:CNKI,Wanfang,PubMed and EMBASE were searched,and the data of 22 patients with CPEO meeting the standards were collected,including 24 patients with two of us.The clinical characteristics,pathological characteristics and gene variation of all patients were sorted and analyzed,and the collected data were analyzed by SPSS 22.0.Results1.Ragged blue fibers(RBF)could be seen in the muscle biopsy of case one.Case one had a heterozygous mutation of c.798T>G(p.F266L)in POLG2 gene.Through family verification,it is found that the father of case one was the carrier of c.798T>G(p.F266L)heterozygous mutation of POLG2 gene.But the father had no clinical symptoms,which suggested incomplete penetrance of the mutation.The muscle biopsy of case two showed RBF.Case two had a heterozygous mutation of c.1495G>T(p.D499Y)in TWNK gene.Case two’s family verification was not performed due to some restrictions.2.Literature review:a total of 24 patients with nDNA related to CPEO were included in this study,including 6 males(25%)and 18 females(75%),with a male to female ratio of 0.33:1.The age of onset:the minimum age of 13 years and the maximum age of 68 years.Ragged red fibers(RRF)were seen in 16 cases,RBF in 5 cases,intense succinate dehydrogenase(SDH)activity were seen in 5 cases,cytochrome c oxidase(COX)negative muscle fibers in 19 cases.Among the 3 patients with POLG2 gene related CPEO,2 were sporadic CPEO and 1 was autosomal dominant inheritance(ad)CPEO.Among the 21 patients with CPEO caused by TWNK gene mutation,5 were sporadic CPEO and 16 were adCPEO.Conclusion1.The main clinical manifestations of nDNA related to CPEO patients are ptosis and eye movement disorder,and some patients are also accompanied by other symptoms of mitochondrial dysfunction.2.The typical characteristics of muscle biopsy are ragged red fibers,ragged blue fibers and cox negative muscle fibers.3.The new variation of POLG2 gene:c.798T>G(p.F266L)and the new variation of TWNK gene:c.1495G>T(p.D499Y)may be pathogenic.