Analysis of the relationship between mitochondrial DNA deletion and clinical complexity of mitochondrial disease
- Author:
- No author available
- Journal Title:
- National Medical Journal of China
- Issue:
- 42
- DOI:
- 10.3760/cma.j.issn.0376-2491.2015.42.013
- Key Word:
- 基因缺失;线粒体疾病;DNA拷贝数异常;突变;Gene deletion;Mitochondrial diseases;DNA copy number variations;Mutation
Abstract： Objective To analyze the relationship between proportion of mitochondrial DNA 4 977 bp deletion (△mtDNA4977) or copy number in blood and the clinical complexity to find the pathogenesis of mitochondrial disease.Methods A total of 160 patients with mitochondrial disease and 101 healthy controls of Peking University First Hospital from December 2003 to December 2013 were collected in this study.Their peripheral blood showed no hot-point mutation which detected by polymerase chain reaction-restriction fragment length polymorphism.All the patients were divided into younger group (age ＜ 10y) and elder group (1 0y ≤ age ＜ 20y).The incidence of △mtDNA4977 was detected by real-time quantitative PCR.Internal gene was used to calculate the number of mitochondrial DNA in each cell.Statistical analysis were carried out by the independent t-test,one-way ANOVA and Spearman' s bivariate correlation analysis.Results △mtDNA4977 proportion in the younger group was (2.66 ± 0.63) ％ and in the elder group was (3.09 ± 0.74) ％,both of them were higher than that of healthy control group with the same age (the younger group:t =8.57,P ＜ 0.01;the elder group:t =4.38,P ＜ 0.01);△mtDNA4977 copy number per cell in the younger group was (2.79 ± 0.50) copy and in the elder group was (2.97 ± 0.48) copy,both of them were higher than that of healthy control group with the same age (the younger group:t =4.50,P ＜ 0.01;the elder group:t =-3.67,P ＜ 0.01).The △mtDNA4977 proportion was positively correlated with the complexity of the mitochondrial disease (the younger group:r =0.519,P ＜ 0.01;the elder group:r =0.772,P ＜ 0.01).The △mtDNA4977 copy number per cell was positively correlated with the complexity of the mitochondrial disease (the younger group:r =0.389,P ＜ 0.01;the elder group:r =0.607,P ＜ 0.05).However,the total mtDNA copy number per cell was negatively correlated with the complexity of the mitochondrial disease (the younger group:r =-0.260,P ＜ 0.01;the elder group:r =-0.430,P ＜ 0.05).Conclusions The proportion or copy number of △mtDNA4977 or total mtDNA copy number in blood are correlated with the comolexity of mitochondrial diseases,especially the proportion of △mtDNA4977.
- [1]Hui, Liu,Yinan, Ma,Fang, Fang,etc.Wild-Type Mitochondrial DNA Copy Number in Urinary Cells as a Useful Marker for Diagnosing Severity of the Mitochondrial Diseases.[J].2013,8.
- [2]Akbari MH,Dehghan M,Kamalidehghan B,etc.Analysis of mitochondrial ND1 gene in human colorectal cancer.[J].2011,16(1).
- [3]Caliebe A,Nikolaus S,Schwark T,etc.Low level of the mtDNA(4977) deletion in blood of exceptionally old individuals.[J].2010,131(3).
- [4]A, R?tig.Genetics of mitochondrial respiratory chain deficiencies.[J].2014,170(5).
- [5]Tao, Chen,Jing, He,Lijun, Shen,etc.The mitochondrial DNA 4,977-bp deletion and its implication in copy number alteration in colorectal cancer.[J].2011,12.
- [6]Thorburn DR,Chow CW,Cleary MA,etc.Diagnostic criteria for respiratory chain disorders in adults and children.[J].2002,59(9).
- [7]McGrath,J.A.,Robinson,M.K.,Binder,R.L..Skin differences based on age and chronicity of ultraviolet exposure: Results from a gene expression profiling study[J].2012,166(Suppl.2).
- [8]Zullo S,Birch Machin MA,Wittock R,etc.A maternal line study investigating the 4977-bp mitochondrial DNA deletion.[J].2003,38(5).
- [9]Guo D,Rao M,Pereira BJ,etc.Mitochondrial DNA injury and mortality in hemodialysis patients.[J].2009,20(1).
- [10]P. Czarny,A. Seda,M. Wielgorski,etc.Mutagenesis of mitochondrial DNA in Fuchs endothelial corneal dystrophy[J].2014,760.
- [11]Blakely EL,Turnbull D,Tuppen HA.Mitochondrial DNA mutations and human disease.[J].2010,1797(2).
- [12]Cenk, Aral,Mustafa, Akkiprik,Handan, Kaya,etc.Mitochondrial DNA common deletion is not associated with thyroid, breast and colorectal tumors in Turkish patients.[J].2010,33(1).
- [13]Ohnuki, Yuko,Takahashi, Kazumi,Iijima, Eri,etc.Multiple Deletions in Mitochondrial DNA in a Patient with Progressive External Ophthalmoplegia, Leukoencephalopathy and Hypogonadism[J].2014,53(12).
- [14]Szentivanyi K,Zeman J,Magner M,etc.Elevated CSF-lactate is a reliable marker of mitochondrial disorders in children even after brief seizures.[J].2011,15(2).
- [15]Horvath R,Samuels DC,Reeve AK,etc.OPA1 mutations cause cytochrome c oxidase deficiency due to loss of wild-type mtDNA molecules.[J].2010,19(15).
- [16]Monika, Obara-Moszynska,Jaroslaw, Maceluch,Waldemar, Bobkowski,etc.A novel mitochondrial DNA deletion in a patient with Kearns-Sayre syndrome: a late-onset of the fatal cardiac conduction deficit and cardiomyopathy accompanying long-term rGH treatment.[J].2013,13.