Detection of a new case harboring mitochondrial A3243G mutation of MELAS syndrome
Main Article Content
Abstract
Mitochondrial genome A3243G mutation in the tRNALeu(UUR) encodinggene (MTTL)is the main cause of mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS). This mutation exists in heteroplasmic form and severity of the disease is affected by many factors including heteroplasmy level.
In this study, a pediatric proband (female, 8 years old) was found to carry A3243G mutation at 77.6% of heteroplasmy by using PCR-RFLP in combination with real-time PCR. The results of the A3243G mutation analysis of the proband’s family showed that her mother without any symptoms of encephalopathyalso carried the mutation at 7.9% of heteroplasmy whereas the mutation was not found in the proband’s healthy father and healthy sister, indicating that the proband received the A3243G mutation from her mother and the expression of MELAS syndromes depended on the level of heteroplasmy.
References
[2] Park H., Davidson E., King MP, The pathogenic A3243G mutation in human mitochondrial tRNALeu(UUR) decreases the efficiency of aminoacylation, Biochemistry, 42, ( 2003). 958.
[3] Naviaux RK, Developing a systematic approach to the diagnosis and classification of mitochondrial disease, Mitochondrion,4, (2004) 351.
[4] Ma Y., Fang F., Cao Y., Yang Y., Zou L., Zhang Y., Wang S., Zhu S., Xu Y., Pei P., Qi Y Clinical features of mitochondrial DNA m.3243A>G mutation in 47 Chinese families, J Neurol Sci, 291, (2010) 17.
[5] Majamaa K., Moilanen JS., Uimonen S., Remes AM., Salmela PI., Kärppä M, Epidemiology of A3243G, the mutation for mitochondrial encepalooomyopathy, lactic acidosis, and stroke-like episodes: prevalence of the mutation in an adult population, Am J Hum Genet, 63, (1998) 447.
[6] Ma Y., Fang F., Yang Y., Zou L., Zhang Y., Wang S., Xu Y., Pei P., Qi Y, The study of mitochondrial A3243G mutation in different samples, Mitochondrion, 9, (2009) 139.
[7] Truong TH., Nguyen TVA., Nguyen VL., Pham VA., Phan TN, Screening of common point-mutations and discovery of new T14727C change in mitochondrial genome of Vietnamese encephalomyopathy patients, Mit DNA, 27, (2016) 441.
[8] Cao Y., Ma Y., Zhang Y., Li Y., Fang F., Wang S., Bu D., Xu Y., Pei P., Li L., Xiao Y., Wu H., Yang Y., Zou L., Qi Y, Detection of eight frequently encountered point mutations in mitochondria in Chinese patients suggestive of mitochondrial encephalomyopathies, Mitochondrion, 10, (2010) 330.
[9] Chae JH., Hwang H., Lim BC., Cheong HI., Hwang YS., Kim KJ, Clinical features of A3243G mitochondrial tRNA mutation. Brain Dev, 26, (2004) 459.
[10] Gal A., Komlosi K., Maasz A., Pentelenyi P., Remenyi V., Ovary C., Valikovics A., Dioszeghy P., Bereczki1 D., Melegh B., Molnár MJ, Analysis of mtDNA A3243G mutation frequency in Hungary, Cent Eur J Med, 5, (2010) 322.
[11] Nagata H., Kumahara K., Tomemori T., Arimoto Y., Isoyama K., Yoshida K., Konno A,Frequency and clinical features of patients with sensorineural hearing loss associated with the A3243G mutation of the mitochondrial DNA in otorhinolaryngic clinics, J Hum Genet, 46, (2001) 595.
[12] Qi Y., Zhang Y., Wang Z., Yang Y., Yuan Y., Niu S., Pei P., Wang S., Ma Y., Bu D., Zou L., Fang F., Xiao J., Sun F., Zhang Y., Wu Y., Wang S., Xiong H., Wu X, Screening of common mitochondrial mutations in Chinese patients with mitochondrial encephalomyopathies. Mitochondrion, 7, (2007) 147.
[13] Truong TH., Nguyen TVA., Nguyen THL., Pham VA., Phan TN, Sensitive quantitation of mitochoncirial mutation using new Taqman probes, Cent Eur J Med, 9, (2014) 839.