Mild clinical manifestation and unusual recovery upon coenzyme Q10 treatment in the first Chinese Leigh syndrome pedigree with mutation m.10197 G>A

被引:17
作者
Chen, Zhiting [1 ]
Zhao, Zhenhua [2 ]
Ye, Qinyong [1 ]
Chen, Ying [1 ]
Pan, Xiaodong [1 ]
Sun, Bin [3 ]
Huang, Huapin [1 ]
Zheng, An [1 ]
机构
[1] Fujian Med Univ, Dept Neurol, Union Hosp, Fuzhou 350001, Fujian, Peoples R China
[2] Fujian Med Univ, Fujian Prov Hosp, Dept Neurol, Fuzhou 350001, Fujian, Peoples R China
[3] Fujian Med Univ, Union Hosp, Dept MR & CT, Fuzhou 350001, Fujian, Peoples R China
关键词
Leigh syndrome; maternally inherited; mitochondrial disease; phenotype; mutation; treatment; COMPLEX-I DEFICIENCY; MITOCHONDRIAL HAPLOGROUP N9A; HEREDITARY OPTIC NEUROPATHY; DNA MUTATION; DISEASE; EXPRESSION; CHILDREN; SEQUENCE; MTDNA;
D O I
10.3892/mmr.2014.2911
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The Leigh syndrome (LS), characterized by psychomotor retardation, seizures, nystagmus, ophthal-moparesis, optic atrophy, ataxia, dystonia, or respiratory failure, is one of the most severe mitochondrial diseases. In the majority of cases, the disease is fatal and patients die before age 5. Mutation m.10197 G>A was found to relate to the severe phenotype of the Leigh syndrome. Here, we describe the first Chinese Leigh syndrome pedigree with this mutation. The proband had the characteristic brain lesions of the Leigh syndrome and presented a decrease in exercise tolerance and mild face paralysis. Sequencing the NADH dehydrogenase, subunit 3 (ND3) gene in the pedigree, revealed that the proband, as well as her unaffected brother, have a high mutant load in the ND3 gene, compared to their mother. Following one-year treatment with the coenzyme Q(10), an obvious improvement in clinical features was observed by magnetic resonance imaging (MRI) in the proband. Our study and previous reports highlight the variability of phenotypic expression of the m.10197 G>A mutation, and suggest that pathogenesis of the syndrome may be affected by a number of factors. This is the first report on successful treatment of an LS patient carrying the mutation m.10197 G>A with the coenzyme Q(10), indicating that Q(10) may attenuate the mitochondrial dysfunctions caused by the m.10197 G>A mutation.
引用
收藏
页码:1956 / 1962
页数:7
相关论文
共 27 条
[1]   SEQUENCE AND ORGANIZATION OF THE HUMAN MITOCHONDRIAL GENOME [J].
ANDERSON, S ;
BANKIER, AT ;
BARRELL, BG ;
DEBRUIJN, MHL ;
COULSON, AR ;
DROUIN, J ;
EPERON, IC ;
NIERLICH, DP ;
ROE, BA ;
SANGER, F ;
SCHREIER, PH ;
SMITH, AJH ;
STADEN, R ;
YOUNG, IG .
NATURE, 1981, 290 (5806) :457-465
[2]   Reanalysis and revision of the Cambridge reference sequence for human mitochondrial DNA [J].
Andrews, RM ;
Kubacka, I ;
Chinnery, PF ;
Lightowlers, RN ;
Turnbull, DM ;
Howell, N .
NATURE GENETICS, 1999, 23 (02) :147-147
[3]   Mutant NDUFS3 subunit of mitochondrial complex I causes Leigh syndrome [J].
Bénit, P ;
Slama, A ;
Cartault, F ;
Giurgea, I ;
Chretien, D ;
Lebon, S ;
Marsac, C ;
Munnich, A ;
Rötig, A ;
Rustin, P .
JOURNAL OF MEDICAL GENETICS, 2004, 41 (01) :14-17
[4]   A novel ND3 mitochondrial DNA mutation in three Korean children with basal ganglia lesions and complex I deficiency [J].
Chae, Jong Hee ;
Lee, Jin Sook ;
Kim, Ki Joong ;
Hwang, Yong Seung ;
Bonilla, Eduardo ;
Tanji, Kurenai ;
Hirano, Michio .
PEDIATRIC RESEARCH, 2007, 61 (05) :622-624
[5]   Mitochondrial complex I deficiency: from organelle dysfunction to clinical disease [J].
Distelmaier, Felix ;
Koopman, Werner J. H. ;
van den Heuvel, Lambertus P. ;
Rodenburg, Richard J. ;
Mayatepek, Ertan ;
Willems, Peter H. G. M. ;
Smeitink, Jan A. M. .
BRAIN, 2009, 132 :833-842
[6]   Coenzyme Q is an obligatory cofactor for uncoupling protein function [J].
Echtay, KS ;
Winkler, E ;
Klingenberg, M .
NATURE, 2000, 408 (6812) :609-613
[7]   Leigh and Leigh-Like Syndrome in Children and Adults [J].
Finsterer, Josef .
PEDIATRIC NEUROLOGY, 2008, 39 (04) :223-235
[8]   Mitochondrial haplogroup N9a confers resistance against type 2 diabetes in Asians [J].
Fuku, Noriyuki ;
Park, Kyong Soo ;
Yamada, Yoshiji ;
Nishigaki, Yutaka ;
Cho, Young Min ;
Matsuo, Hitoshi ;
Segawa, Tomonori ;
Watanabe, Sachiro ;
Kato, Kimihiko ;
Yokoi, Kiyoshi ;
Nozawa, Yoshinori ;
Lee, Hong Kyu ;
Tanaka, Masashi .
AMERICAN JOURNAL OF HUMAN GENETICS, 2007, 80 (03) :407-415
[9]   Clinical expression of Leber hereditary optic neuropathy is affected by the mitochondrial DNA-haplogroup background [J].
Hudson, Gavin ;
Carelli, Valerio ;
Spruijt, Liesbeth ;
Gerards, Mike ;
Mowbray, Catherine ;
Achilli, Alessandro ;
Pyle, Angela ;
Elson, Joanna ;
Howell, Neil ;
La Morgia, Chiara ;
Valentino, Maria Lucia ;
Huoponen, Kirsi ;
Savontaus, Marja-Liisa ;
Nikoskelainen, Eeva ;
Sadun, Alfredo A. ;
Salomao, Solange R. ;
Belfort, Rubens, Jr. ;
Griffiths, Philip ;
Man, Patrick Yu Wai ;
de Coo, Rene F. M. ;
Horvath, Rita ;
Zeviani, Massimo ;
Smeets, Hubert J. T. ;
Torroni, Antonio ;
Chinnery, Patrick F. .
AMERICAN JOURNAL OF HUMAN GENETICS, 2007, 81 (02) :228-233
[10]   Gene Expression Pattern in Transmitochondrial Cytoplasmic Hybrid Cells Harboring Type 2 Diabetes-Associated Mitochondrial DNA Haplogroups [J].
Hwang, Seungwoo ;
Kwak, Soo Heon ;
Bhak, Jong ;
Kang, Hae Sun ;
Lee, You Ri ;
Koo, Bo Kyung ;
Park, Kyong Soo ;
Lee, Hong Kyu ;
Cho, Young Min .
PLOS ONE, 2011, 6 (07)