Case Report

A Patient with MELAS Syndrome Carried an M.3243A>G Mutation in Mitochondrial DNA and Multiple Nuclear Genetic Variants: A Case Report

Abstract

We discuss the involvement of nuclear genetic variants correlating to observed phenotype in this case study. In January 2020, the 19-year-old boy from Nantong, Jiangsu Province, China with epilepsy symptom was identified to have myelin loss in the motor and sensory nerves in the electromyogram examination. Brain magnetic resonance imaging (MRI) demonstrated high-intensity areas of small multifocal gray matter regions in the bilateral temporal, parietal, and occipital lobes. In the serum of the patient, the levels of lactate dehydrogenase (LDH) and lactic acid were higher than the normal range values in multiple tests. By subsequent whole exome sequencing (WES) including analysis of the mitochondrial genome, the patient was revealed to carry an m.3243A>G mutation in mitochondria MTTL1 gene which was confirmed by direct Sanger sequencing analysis. Thus, disease of the patient was diagnosed as mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome. According to WES analysis, the patient also carried multiple homozygous variants, which correlating to myelinloss and epilepsy in nuclear genes. The peripheral neuropathy of the patient carrying single mitochondrial m.3243A>G mutation could be caused by multiple nuclear DNA defect.

 

1. Haast RAM, Ivanov D, IJsselstein RJT, et al (2018). Anatomic & metabolic brain markers of the m.3243A>G mutation: A multi-parametric 7T MRI study. Neuroimage Clin, 18:231-244.
2. Santa KM (2010). Treatment options for mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome. Pharmacotherapy, 30(11):1179-1196.
3. de Laat P, Koene S, Heuvel LP, Rodenburg RJ, Janssen MC, Smeitink JA (2013). Inheritance of the m.3243A>G mutation. JIMD Rep, 8:47-50.
4. Lax NZ, Hepplewhite PD, Reeve AK, et al (2012). Cerebellar ataxia in patients with mitochondrial DNA disease: a molecular clinicopathological study. J Neuropathol Exp Neurol, 71(2):148-161.
5. Conrad K, Schneider H, Ziemssen T, et al (2007). A new line immunoassay for the multiparametric detection of antiganglioside autoantibodies in patients with autoimmune peripheral neuropathies. Ann N Y Acad Sci, 1109:256-264.
6. Kuijf M, Ruts L, van Doorn PA, Koudstaal PJ, Jacobs BC (2009). Diagnostic value of anti-GQ1b antibodies in a patient with relapsing dysarthria and ataxia. BMJ Case Rep, 2009.
7. Geng X, Zhang Y, Yan J, et al (2019). Mitochondrial DNA mutation m.3243A>G is associated with altered mitochondrial function in peripheral blood mononuclear cells, with heteroplasmy levels and with clinical phenotypes. Diabet Med, 36(6):776-783.
8. Karppa M, Syrjala P, Tolonen U, Majamaa K (2003). Peripheral neuropathy in patients with the 3243A>G mutation in mitochondrial DNA. J Neurol, 250(2):216-221.
9. Nesbitt V, Pitceathly RD, Turnbull DM, et al (2013). The UK MRC Mitochondrial Disease Patient Cohort Study: clinical phenotypes associated with the m.3243A>G mutation--implications for diagnosis and management. J Neurol Neurosurg Psychiatry, 84(8):936-938.
10. Michailov GV, Sereda MW, Brinkmann BG, et al (2004). Axonal neuregulin-1 regulates myelin sheath thickness. Science, 304(5671):700-703.
11. Mei L, Nave KA (2014). Neuregulin-ERBB signaling in the nervous system and neuropsychiatric diseases. Neuron, 83(1):27-49.
12. Mei L, Xiong WC (2008). Neuregulin 1 in neural development, synaptic plasticity and schizophrenia. Nat Rev Neurosci, 9(6):437-452.
13. Hong LE, Wonodi I, Stine OC, Mitchell BD, Thaker GK (2008). Evidence of missense mutations on the neuregulin 1 gene affecting function of prepulse inhibition. Biol Psychiatry, 63(1):17-23.
14. Park J, Hyun YS, Kim YJ, et al (2013). Exome Sequencing Reveals a Novel PRPS1 Mutation in a Family with CMTX5 without Optic Atrophy. J Clin Neurol, 9(4):283-288.
15. Whittaker RG, Devine HE, Gorman GS, et al (2015). Epilepsy in adults with mitochondrial disease: A cohort study. Ann Neurol, 78(6):949-957.
16. Aridon P, Marini C, Di Resta C, et al (2006). Increased sensitivity of the neuronal nicotinic receptor alpha 2 subunit causes familial epilepsy with nocturnal wandering and ictal fear. Am J Hum Genet, 79(2):342-350.
Files
IssueVol 51 No 12 (2022) QRcode
SectionCase Report(s)
DOI https://doi.org/10.18502/ijph.v51i12.11473
Keywords
Mitochondrial DNA mutation MELAS Syndrome Epilepsy Myelinloss Case report
Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
1.
Chu X, Dai J, Cui H, Shen H, Wu Q, Zhu X, Zhu B. A Patient with MELAS Syndrome Carried an M.3243A>G Mutation in Mitochondrial DNA and Multiple Nuclear Genetic Variants: A Case Report. Iran J Public Health. 2022;51(12):2817-2825.