The clinical and genetic characteristics in children with mitochondrial disease in China
Mitochondrial disease was a clinically and genetically heterogeneous group of diseases, thus the diagnosis was very difficult to clinicians. Our objective was to analyze clinical and genetic characteristics of children with mitochondrial disease in China. We tested 141 candidate patients who have been suspected of mitochondrial disorders by using targeted next-generation sequencing (NGS), and summarized the clinical and genetic data of gene confirmed cases from Neurology Department, Beijing Children’s Hospital, Capital Medical University from October 2012 to January 2015. In our study, 40 cases of gene confirmed mitochondrial disease including eight kinds of mitochondrial disease, among which Leigh syndrome was identified to be the most common type, followed by mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS). The age-of-onset varies among mitochondrial disease, but early onset was common. All of 40 cases were gene confirmed, among which 25 cases (62.5%) with mitochondrial DNA (mtDNA) mutation, and 15 cases (37.5%) with nuclear DNA (nDNA) mutation. M.3243A>G (n=7) accounts for a large proportion of mtDNA mutation. The nDNA mutations include SURF1 (n=7), PDHA1 (n=2), and NDUFV1, NDUFAF6, SUCLA2, SUCLG1, RRM2B, and C12orf65, respectively.
Keywordsmitochondrial disease targeted next generation sequencing clinical features gene
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The authors greatly appreciate the cooperation of all the patients and their families, and are grateful to MyGenomics and SinoPath for their technical support and services.
- Calvo, S.E., Compton, A.G., Hershman, S.G., Lim, S.C., Lieber, D.S., Tucker, E.J., Laskowski, A., Garone, C., Liu, S., Jaffe, D.B., Christodoulou, J., Fletcher, J.M., Bruno, D.L., Goldblatt, J., Dimauro, S., Thorburn, D.R., and Mootha, V.K. (2012). Molecular diagnosis of infantile mitochondrial disease with targeted next-generation sequencing. Sci Transl Med 4, 118ra110.CrossRefGoogle Scholar
- Chinnery, P.F. (1993). Mitochondrial Disorders Overview. In GeneReviews R.A. Pagon, M.P. Adam, H.H. Ardinger, S.E. Wallace, A. Amemiya, L.J.H. Bean, T.D. Bird, N. Ledbetter, H.C. Mefford, R.J.H. Smith, et al., eds. (Seattle: University of Washington, Seattle).Google Scholar
- Di Mauro, S., and Hirano, M. (1993). MERRF. In GeneReviews(R), R.A. Pagon, M.P. Adam, H.H. Ardinger, S.E. Wallace, A. Amemiya, L.J.H. Bean, T.D. Bird, N. Ledbetter, H.C. Mefford, R.J.H. Smith, et al., eds. (Seattle: University of Washington, Seattle).Google Scholar
- Lebre, A.S., Rio, M., Faivre d’Arcier, L., Vernerey, D., Landrieu, P., Slama, A., Jardel, C., Laforêt, P., Rodriguez, D., Dorison, N., Galanaud, D., Chabrol, B., Paquis-Flucklinger, V., Grévent, D., Edvardson, S., Steffann, J., Funalot, B., Villeneuve, N., Valayannopoulos, V., de Lonlay, P., Desguerre, I., Brunelle, F., Bonnefont, J.P., Rötig, A., Munnich, A., and Boddaert, N. (2011). A common pattern of brain MRI imaging in mitochondrial diseases with complex I deficiency. J Med Genets 48, 16–23.CrossRefGoogle Scholar
- Lieber, D.S., Calvo, S.E., Shanahan, K., Slate, N.G., Liu, S., Hershman, S.G., Gold, N.B., Chapman, B.A., Thorburn, D.R., Berry, G.T., Schmahmann, J.D., Borowsky, M.L., Mueller, D.M., Sims, K.B., and Mootha, V.K. (2013). Targeted exome sequencing of suspected mitochondrial disorders. Neurology 80, 1762–1770.CrossRefPubMedPubMedCentralGoogle Scholar
- Neveling, K., Collin, R.W.J., Gilissen, C., van Huet, R.A.C., Visser, L., Kwint, M.P., Gijsen, S.J., Zonneveld, M.N., Wieskamp, N., de Ligt, J., Siemiatkowska, A.M., Hoefsloot, L.H., Buckley, M.F., Kellner, U., Branham, K.E., den Hollander, A.I., Hoischen, A., Hoyng, C., Klevering, B.J., van den Born, L.I., Veltman, J.A., Cremers, F.P.M., and Scheffer, H. (2012). Next-generation genetic testing for retinitis pigmentosa. Hum Mutat 33, 963–972.CrossRefPubMedPubMedCentralGoogle Scholar
- Pagliarini, D.J., Calvo, S.E., Chang, B., Sheth, S.A., Vafai, S.B., Ong, S.E., Walford, G.A., Sugiana, C., Boneh, A., Chen, W.K., Hill, D.E., Vidal, M., Evans, J.G., Thorburn, D.R., Carr, S.A., and Mootha, V.K. (2008). A mitochondrial protein compendium elucidates complex I disease biology. Cell 134, 112–123.CrossRefPubMedPubMedCentralGoogle Scholar
- Pulkes, T., Eunson, L., Patterson, V., Siddiqui, A., Wood, N.W., Nelson, I.P., Morgan-Hughes, J.A., and Hanna, M.G. (1999). The mitochondrial DNA G13513A transition in ND5 is associated with a LHON/MELAS overlap syndrome and may be a frequent cause of MELAS. Ann Neurol 46, 916–919.CrossRefPubMedGoogle Scholar
- Shanske, S., Coku, J., Lu, J., Ganesh, J., Krishna, S., Tanji, K., Bonilla, E., Naini, A.B., Hirano, M., and DiMauro, S. (2008). The G13513A mutation in the ND5 gene of mitochondrial DNA as a common cause of MELAS or Leigh syndrome: evidence from 12 cases. Arch Neurol 65, 368–372.CrossRefPubMedGoogle Scholar
- Thorburn, D.R., and Rahman, S. (1993). Mitochondrial DNA-associated Leigh Syndrome and NARP. In GeneReviews(R), R.A. Pagon, M.P. Adam, H.H. Ardinger, S.E. Wallace, A. Amemiya, L.J.H. Bean, T.D. Bird, N. Ledbetter, H.C. Mefford, R.J.H. Smith, et al., eds. (Seattle: University of Washington, Seattle).Google Scholar
- Valayannopoulos, V., Haudry, C., Serre, V., Barth, M., Boddaert, N., Arnoux, J.B., Cormier-Daire, V., Rio, M., Rabier, D., Vassault, A., Munnich, A., Bonnefont, J.P., de Lonlay, P., Rö tig, A., and Lebre, A.S. (2010). New SUCLG1 patients expanding the phenotypic spectrum of this rare cause of mild methylmalonic aciduria. Mitochondrion 10, 335–341.CrossRefPubMedGoogle Scholar