6个线粒体脑肌病伴高乳酸血症和卒中样发作综合征(MELAS)家系先证者线粒体基因全序列比较分析

doi:10.3724/SP.J.1005.2014.1159

[an error occurred while processing this directive]

HEREDITAS(Beijing) ›› 2014, Vol. 36 ›› Issue (11): 1159-1167.doi: 10.3724/SP.J.1005.2014.1159

• Research Articles • Previous Articles Next Articles

Mitochondrial genome analysis in the probands of six Chinese families with MELAS

Li Liu¹, Yuquan Shao², Baorong Zhang³, Pingping Jiang¹, Ailian Du^{3, 4}, Minxin Guan¹

1. Institute of Genetics, College of Life Science, Zhejiang University, Hangzhou 310058, China;
2. Department of Neurology, Sir Run Run Shao Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China;
3. Department of Neurology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China;
4. Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China

Received:2014-04-04 Online:2014-11-20 Published:2014-10-28

Abstract

Abstract: Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) is a genetically heterogeneous disorder. The most prevalent mitochondrial DNA (mtDNA) mutation associated with MELAS is the m.3243A>G transition in the mitochondrial tRNA^Leu(UUR) gene. Here, we report the clinical, genetic and molecular characterization of six probands from Han Chinese families with MELAS. Four of six probands carried the heteroplasmic m.3243A>G mutation. The levels of mutation load ranged from 29% to 59%, which were correlated with the severity of the clinical phenotypes. Two probands with MELAS/Leigh overlap were 3243 A>G negative, whose severity and relapse were greater than the other 4 probands. One proband with MELAS/Leigh harbored the known ND5 m.13094T>C mutation, which is related to MELAS/Leigh overlap and cerebella ataxia. Sequence analysis of entire mtDNA showed the distinct sets of variants including some variants that may be associated with diabetes, hearing loss, seizures, cardiomyopathy, and Leigh syndrome. Our data suggested that the phenotype and severity of MELAS mainly depend on the mutation load, and some variants may partially contribute to the phenotype and diversity. Our finding also highlighted the complexity of the relationship between genotype and phenotype in MELAS.

Key words: mitochondrial DNA, MELAS, polymorphism, phenotype

Li Liu, Yuquan Shao, Baorong Zhang, Pingping Jiang, Ailian Du, Minxin Guan. Mitochondrial genome analysis in the probands of six Chinese families with MELAS[J]. HEREDITAS(Beijing), 2014, 36(11): 1159-1167.

References

[1] SG, Phillips PC, DiMauro S, De Vivo DC, Rowland LP. Mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes: a distinctive clinical syndrome. Ann Neurol , 1984, 16(4): 481–488.
[2] Y, Horai S, Matsuoka T, Koga Y, Nihei K, Kobayashi M, Nonaka I. Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS): a correlative study of the clinical features and mitochondrial DNA mutation. Neurology , 1992, 42(3): 545–550.
[3] A Human Mitochondrial Genome Database. http://www.mitomap.org, 2014.
[4] S, Pallotti F, La Morgia C, Valentino ML, Pierangeli G, Cortelli P, Baruzzi A, Montagna P, Carelli V. High frequency of migraine-only patients negative for the 3243 A>G tRNA Leu mtDNA mutation in two MELAS families. Cephalalgia , 2010, 30(8): 919–927.
[5] MJ, Taylor SL, Tobe VO, Nickerson DA. Automating the identification of DNA variations using quality-based fluorescence re-sequencing: analysis of the human mitochondrial genome. Nucleic Acids Res , 1998, 26(4): 967–973.
[6] RM, Kubacka I, Chinnery PF, Lightowlers RN, Turnbull DM, Howell N. Reanalysis and revision of the Cambridge reference sequence for human mitochondrial DNA. Nat Genet , 1999, 23(2): 147.
[7] A, Ronchi D, Bordoni A, Bordo B, Lanfranconi S, Bellotti MG, Corti S, Lucchini V, Sciacco M, Moggio M, Baron P, Comi GP, Colombo A, Bersano A, on behalf of Lombardia GENS collaborators. POLG1 mutations and stroke like episodes: a distinct clinical entity rather than an atypical MELAS syndrome. BMC Neurol , 2013, 13: 8.
[8] V, Hoertnagel K, Carrozzo R, Galimberti C, Munaro M, Granatiero M, Zelante L, Gasparini P, Marzella R, Rocchi M, Bayona-Bafaluy MP, Enriquez JA, Uziel G, Bertini E, Dionisi-Vici C, Franco B, Meitinger T, Zeviani M. Mutations of SURF-1 in Leigh disease associated with cytochrome c oxidase deficiency. Am J Hum Genet , 1998, 63(6): 1609–1621.
[9] L, Piga D, Lamantea E, Carrara F, Uziel G, Cudia P, Zani A, Farina L, Morandi L, Mora M, Spinazzola A, Zeviani M, Tiranti V. Identification of novel mutations in five patients with mitochondrial encephalomyopathy. Biochim Biophys Acta , 2009, 1787(5): 491–501.
[10] NZ, Hepplewhite PD, Reeve AK, Nesbitt V, McFarland R, Jaros E, Taylor RW, Turnbull DM. Cerebellar ataxia in patients with mitochondrial DNA disease: a molecular clinicopathological study. J Neuropathol Exp Neurol , 2012, 71(2): 148–161.
[11] RH, Guan MX. Human mitochondrial Leucyl-tRNA synthetase corrects mitochondrial dysfunctions due to the tRNA Leu(UUR) A3243G mutation, associated with mitoch-ondrial encephalomyopathy, lactic acidosis, and stroke- like symptoms and diabetes. Mol Cell Biol , 2010, 30(9): 2147–2154.
[12] I, Alila-Fersi O, Mkaouar-Rebai E, Aloulou H, Kifagi C, Hachicha M, Fakhfakh F. A novel m.12908T>A mutation in the mitochondrial ND5 gene in patient with infantile-onset Pompe disease. Biochem Biophys Res Commun , 2012, 429(1–2): 31–38.
[13] S. Mitochondrial encephalomyopathies: gene mutation. Neuromuscul Disord , 2004, 14(1): 107–116.
[14] Z, Liu S, Yang Y, Yuan Y, Wu L, Qi Y, Chen Q. Detection of A3243G point mutation in mitochondrial DNA from 10 cases of MELAS. Chin Med J (Engl) , 2002, 115(7): 995–997.
[15] PF, Howell N, Lightowlers RN, Turnbull DM. Molecular pathology of MELAS and MERRF.the rela-tionship between mutation load and clinical phenotypes. Brain , 1997, 120(10): 1713–1721.
[16] JF, Parisi MA, Bennett JL, Clayton DA. Impairment of mitochondrial transcription termination by a point mutation associated with the MELAS subgroup of mito-chondrial encephalomyopathies. Nature , 1991, 351(6323): 236–239.
[17] JX, Wang DW, Li RH, Li WX, Ji JZ, Zhao J, Ye W, Yang L, Qian YP, Zhu Y, Guan MX. Maternally transmitted diabetes mellitus associated with the mitochondrial tRNA Leu(UUR) A3243G mutation i

Metrics

Comments

www.chinagene.cn
备案号：京ICP备09063187号

Mitochondrial genome analysis in the probands of six Chinese families with MELAS

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 15

Recommended Articles

Metrics

Comments

[1]	Ruijia Song, Lu Han, Haifeng Sun, Bin Shen. Advances in mitochondrial DNA base editing technology [J]. Hereditas(Beijing), 2023, 45(8): 632-642.
[2]	Yan Hao, Fumin Lei. Genetic mechanism of adaptive evolution: the example of adaptation to high altitudes [J]. Hereditas(Beijing), 2022, 44(8): 635-654.
[3]	Xueqian Wang, Qingzhen Zhang, Peng Cheng, Tingting Dong, Weiguo Li, Zhe Zhou, Shengqi Wang. Genetic polymorphisms of 66 InDel loci in the Chinese Han population [J]. Hereditas(Beijing), 2022, 44(4): 335-345.
[4]	Tian Shu, Haochang Hu, Caijie Shen, Shaoyi Lin, Xiaomin Chen. Research progress of the correlation between genotype and phenotype in hypertrophic cardiomyopathy [J]. Hereditas(Beijing), 2022, 44(3): 198-207.
[5]	Meng Fu, Yan Li. The origin and domestication history of domestic horses and the domestication characteristics of breeds [J]. Hereditas(Beijing), 2022, 44(3): 216-229.
[6]	Wenjing Zhu, Zhiwei Liu. MDMPR: Mouse Developmental and Metabolic Phenotype Repository [J]. Hereditas(Beijing), 2021, 43(4): 375-384.
[7]	Yanyan Cao, Miaomiao Cheng, Fang Song, Yujin Qu, Jinli Bai, Hong Wang. Familial study of spinal muscular atrophy carriers with SMN1 (2+0) genotype [J]. Hereditas(Beijing), 2021, 43(2): 160-168.
[8]	Haoyu Wang, Yuhan Hu, Yueyan Cao, Qiang Zhu, Yuguo Huang, Xi Li, Ji Zhang. AI-SNPs screening based on the whole genome data and research on genetic structure differences of subcontinent populations [J]. Hereditas(Beijing), 2021, 43(10): 938-948.
[9]	Xiaohong He, Lin Jiang, Yabin Pu, Qianjun Zhao, Yuehui Ma. Progress on genetic mapping and genetic mechanism of cattle and sheep horns [J]. Hereditas(Beijing), 2021, 43(1): 40-51.
[10]	Yuzhuo Wang, Yiming Zhang, Xiaolian Dong, Xuecai Wang, Jianfu Zhu, Na Wang, Feng Jiang, Yue Chen, Qingwu Jiang, Chaowei Fu. Modification effects of T2DM-susceptible SNPs on the reduction of blood glucose in response to lifestyle interventions [J]. Hereditas(Beijing), 2020, 42(5): 483-492.
[11]	Qing Zhang,Jie Ping,Haoxiang Zhang,Bo Kang, ,Gangqiao Zhou. Genetic association of MKL1 gene polymorphisms with the high-altitude adaptation [J]. Hereditas(Beijing), 2019, 41(7): 634-643.
[12]	Weijuan Hu, Hong-Qing Ling, Xiangdong Fu. Development and application of the plant phenomics analysis platform [J]. Hereditas(Beijing), 2019, 41(11): 1060-1066.
[13]	Yujie Wang, Xiaokun Zhou, Dan Xu. Update on autosomal recessive primary microcephaly (MCPH)-associated proteins [J]. Hereditas(Beijing), 2019, 41(10): 905-918.
[14]	Jieyu Zhang,Yanan Chu,Bingjie Zou,Yanjie Zhang,Liying Feng. Detection of UGT1A16* single nucleotide polymorphism in oral swap samples using the cascade invader assay-based real-time PCR [J]. Hereditas(Beijing), 2018, 40(8): 668-675.
[15]	Xiaowei Meng, Jie Wang, Qingwen Ma. The genetic background and application of Down syndrome mouse models [J]. Hereditas(Beijing), 2018, 40(3): 207-217.