Skip to content
BY-NC-ND 3.0 license Open Access Published by De Gruyter Open Access April 9, 2010

Analysis of mtDNA A3243G mutation frequency in Hungary

  • Aniko Gal EMAIL logo , Katalin Komlosi , Anita Maasz , Klara Pentelenyi , Viktoria Remenyi , Csaba Ovary , Attila Valikovics , Peter Dioszeghy , Daniel Bereczki , Bela Melegh and Maria Molnár
From the journal Open Medicine


The A3243G mutation in the mitochondrial tRNALeu (UUR) gene is one of the most common causes of mitochondrial DNA related disorders. Originally it was described in MELAS syndrome (Mitochondrial Encephalomyopathy, Lactic acidosis, Stroke-like episodes), later it had been found to be associated with various phenotypes. In our study the mutation frequency of the A3243G mtDNA mutation was investigated in patients with maternal sensoneural hearing loss, stroke-like episodes, ataxia and myopathy with undetermined etiology. We screened 631 Hungarian patients in North-East, South-West and Central Hungary between 1999 and 2008 for this mutation. The mtDNA analysis was performed from blood and/or muscle tissue. The A3243G substitution was present in 6 patients in heteroplasmic form. The segregation analysis detected 8 further cases. The frequency of the A3243G mutation was 2.22% in the investigated patients. The A3243G mutation frequency in Hungary does not differ significantly from other countries using similar patient selection criteria, however in Finland a higher mutation rate was found. In studies investigated the mutation frequency of this mutation in diabetes mellitus similarly wide variety was detected as well. We conclude that the study design has a huge impact on the result of the genetic epidemiological investigation analyzing the mutation frequency of the A3243G mutation due to the broad clinical phenotype and the different mutation load in different tissues.

[1] Goto Y.l., Nonaka I., Horai S., A mutation in the tRNALeu (UUR) gene associated with the MELAS subgroup of mitochondrial encephalomyopathies, Nature, 1990, 348, 651–653 in Google Scholar

[2] Finsterer J., Genetic, pathogenetic, and phenotypic implications of the mitochondrial A3243G tRNALeu(UUR) mutation, Acta Neurol Scand., 2007, 116, 1–14 in Google Scholar

[3] Moraes C.T., Ciacci F., Silvestri G., Shanske S., Sciacco M., Hirano M. et al., Atypical clinical presentations associated with the MELAS mutation at position 3243 of human mitochndrial DNA, Neuromuscul. Disord., 1993, 3, 43–50 in Google Scholar

[4] Klemm T., Neumann S., Trülzsch B., Pistrosch F., Hanefeld M., Paschke R., Search for mitochondrial DNA mutation at position 3243 in German patients with a positive family history of maternal diabetes mellitus, Exp. Clin. Endocrinol. Diabetes., 2001, 109, 283–287 in Google Scholar PubMed

[5] Majamaa K., Moilanen J.S., Uimonen S., Remes A.M., Salmela P.I., Kärppä M. et al., Epidemiology of A3243G, the mutation for mitochondrial encepalooomyopathy, lactic acidosis, and strokelike episodes: prevalence of the mutation in an adult population, Am. J. Hum. Genet., 1998, 63, 447–454 in Google Scholar PubMed PubMed Central

[6] Majamaa K., Turkka J., Karppa M., Winqvist S., Hassinen I.E., The common MELAS mutation A3243G in mitochondrial DNA among young patients with an occipital brain infarct, Neurology, 1997, 49, 1331–1334 10.1212/WNL.49.5.1331Search in Google Scholar PubMed

[7] Salles J.E., Kasamatsu T.S., Dib S.A., Moisés R.S., Beta-cell function in individuals carrying the mitochondrial tRNA leu (UUR) mutation, Pancreas., 2007, 34, 133–137 in Google Scholar PubMed

[8] Lévêque M., Marlin S., Jonard L., Procaccio V., Reynier P., Amati-Bonneau P. et al, Whole mitochondrial genome screening in maternally inherited non-syndromic hearing impairment using a microarray resequencing mitochondrial DNA chip, Eur. J. Hum. Genet., 2007, 15, 1145–55 in Google Scholar PubMed

[9] Sternberg D., Chatzoglou E., Laforêt P., Fayet G., Jardel C., Blondy P. et al, Mitochondrial DNA transfer RNA gene sequence variations in patients with mitochondrial disorders, Brain, 2001, 124, 984–994 in Google Scholar PubMed

[10] Nagata H., Kumahara K., Tomemori T., Arimoto Y., Isoyama K., Yoshida K. et al., 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., 2001, 46, 595–599 in Google Scholar PubMed

[11] Lee Y.C., Lu Y.C., Chang M.H., Soong B.W., Common mitochondrial DNA and POLG1 mutations are rare in the Chinese patients with adult-onset ataxia on Taiwan, J. Neurol. Sci., 2007, 254, 65–68 in Google Scholar PubMed

[12] Taylor R.W., Taylor G.A., Morris C.M., Edwardson J.M., Turnbull D.M., Diagnosis of mitochondrial disease: assessment of mitochondrial DNA heteroplasmy in blood, Biochem. Biophys. Res. Commun., 1998, 251, 883–887 in Google Scholar PubMed

[13] Ohkubo K., Yamano A., Nagashima M., Mori Y., Anzai K., Akehi Y. et al, Mitochondrial gene mutations in the tRNA(Leu(UUR)) region and diabetes: prevalence and clinical phenotypes in Japan, Clin. Chem., 47, 1641–1648 10.1093/clinchem/47.9.1641Search in Google Scholar

[14] Lehto M., Wipemo C., Ivarsson S.A., Lindgren C., Lipsanen-Nyman M., Weng J. et al., High frequency of mutations in MODY and mitochondrial genes in Scandinavian patients with familial early-onset diabetes, Diabetologia, 1999, 42, 1131–1137 in Google Scholar PubMed

[15] Salles J.E., Kalinin L.B., Ferreira S.R., Kasamatsu T., Moisés R.S., Diabetes mellitus associated with the mitochondrial mutation A3243G: frequency and clinical presentation, Arq. Bras. Endocrinol. Metabol., 2007, 51, 559–565, 2007 10.1590/S0004-27302007000400009Search in Google Scholar

[16] Pang C.Y., Huang C.C., Yen M.Y., Wang E.K., Kao K.P., Chen S.S. et al, Molecular epidemiologic study of mitochondrial DNA mutations in patients with mitochondrial diseases in Taiwan, J. Formos. Med. Assoc., 1999, 98, 326–334 Search in Google Scholar

[17] Martin-Kleiner I., Pape-Medvidovic E., Pavlic-Renar I., Metelko Z., Kusec R., Gabrilovac J. et al, Pilot study of mitochondrial DNA point mutation A3243G in a sample of Croatian patients having type 2 diabetes mellitus associated with maternal inheritance, Acta Diabetol., 2004, 41, 179–184 in Google Scholar PubMed

[18] Gal A., Szabó A., Pentelényi K., Szabo A., Pal Z., Maternally inherited diabetes mellitus, deafness, chronic progressive external ophthalmoplegia and myopathy as the result of A3243G mutation of mtDNA, 2008, Orvosi Hetilap, 149, 1593–1598 10.1556/oh.2008.28398Search in Google Scholar PubMed

[19] Mkaouar-Rebai E., Tlili A., Masmoudi S., Belguith N., Charfeddine I., Mnif M. et al, Mutational analysis of the mitochondrial tRNALeu(UUR) gene in Tunisian patients with mitochondrial diseases, Biochem. Biophys. Res. Commun., 2007, 355, 1031–1037 in Google Scholar PubMed

[20] Wang Z.X., Luan X.H., Zhang Y., Yang Y.L., Qi Y., Bu D.F. et al., Mitochondrial DNA mutation analysis in 97 Chinese patients with mitochondrial cephalomyopathy, Zhonghua Yi Xue Za Zhi., 2008, 88, 3254–3256 Search in Google Scholar

[21] Rodríguez-Hernández M., Hirano M., Arrieta T., Lestayo Z., Estrada R., Santiesteban R. et al., Molecular studies in Cuban patients with progressive external ophthalmoplegia, Rev. Neurol., 2000, 30, 1001–1005 Search in Google Scholar

[22] Chae J.H., Hwang H., Lim B.C., Cheong H.I., Hwang Y.S., Kim K.J., Clinical features of A3243G mitochondrial tRNA mutation, Brain Dev., 2004, 26, 459–462 in Google Scholar PubMed

[23] Komlosi K., Kellermayer R., Maasz A., Havasi V., Hollody K., Vincze O. et al, Maternally inherited deafness and unusual phenotypic manifestations associated with A3243G mitochondrial DNA mutation, Pathol. Oncol. Res., 2005, 11, 82–86 in Google Scholar PubMed

[24] Komlosi K., Bene J., Havasi V., Tihanyi M., Herczegfalvi A., Moser J. et. al., Phenotypic variants of A3243G mitochondrial DNA mutation in a Hungarian family. Orv Hetil., 2004, 145, 1805–1809 Search in Google Scholar

[25] Wang C.L., Li F., Hou Q.Z., Li H.Z., Zhang Y., Ning G., Analysis of mitochondrial DNA gene tRNALeu(UUR) A3243G mutation in diabetic pedigrees, Zhonghua Yi Xue Yi Chuan Xue Za Zhi., 2009, 26, 74–77 Search in Google Scholar

[26] Ng M.C., Yeung V.T., Chow C.C., Li J.K., Smith P.R., Mijovic C.H. et al, Mitochondrial DNA A3243G mutation in patients with early- or late-onset type 2 diabetes mellitus in Hong Kong Chinese, Clin. Endocrinol. (Oxf)., 2000, 52, 557–564 in Google Scholar

[27] Francisco G., Hernández C., Martínez R., García-Arumí E., Andreu A., Simó R., Prevalence of mitochondrial A3243G mutation in adult type 1 diabetic patients in Catalonia, Diabetes Metab., 2005, 31, 621–622 in Google Scholar

[28] Zhang X.Y., Zhang S.L., Ke B.S., Jiang Z.S., Sun R., Study on mitochondrial DNA gene tRNA(Leu(UUR)) A3243G mutation in type 2 diabetes mellitus, Zhonghua Yi Xue Yi Chuan Xue Za Zhi., 2004, 21, 168–170 Search in Google Scholar

[29] Zhao J., Ji J.Z., Wang D.W., Zhang J., Wu H.J., Lu J.X., Detecting of mtDNA mutations at position A3243G and G3316A in patients with type 2 diabetes mellitus in Wenzhou, Yi Chuan, 2006, 28, 1206–1212 10.1360/yc-006-1206Search in Google Scholar

[30] Małecki M., Klupa T., Wanic K., Frey J., Cyganek K., Sieradzki J., Search for mitochondrial A3243G tRNA(Leu) mutation in Polish patients with type 2 diabetes mellitus, Med Sci Monit., 2001, 7, 246–250 Search in Google Scholar

[31] Tang D.L., Zhou X., Li X., Zhao L., Liu F., Variation of mitochondrial gene and the association with type 2 diabetes mellitus in a Chinese population, Diabetes Res. Clin. Pract., 2006, 73, 77–82 in Google Scholar

[32] Turner L.F., Kaddoura S., Harrington D., Cooper J.M., Poole-Wilson P.A., Schapira A.H., Mitochondrial DNA in idiopathic cardiomyopathy, Eur. Heart J., 1998, 19, 1725–1729 in Google Scholar

[33] Abad M.M., Cotter P.D., Fodor F.H., Larson S., Ginsberg-Fellner F., Desnick R.J. et al., Screening for the mitochondrial DNA A3243G mutation in children with insulin-dependent diabetes mellitus, Metabolism., 1997, 46, 445–449 in Google Scholar

[34] Marotta R., Chin J., Quigley A., Katsabanis S., Kapsa R., Byrne E. et al., Diagnostic screening of mitochondrial DNA mutations in Australian adults 1990–2001, Intern. Med. J., 2004, 34, 10–19 in Google Scholar PubMed

[35] Zhang Y., Yang Y.L., Sun F., Cai X., Qian N., Yuan Y. et al., Clinical and molecular survey in 124 Chinese patients with Leigh or Leigh-like syndrome, J. Inherit. Metab. Dis., 2007, 30, 265 in Google Scholar PubMed

Published Online: 2010-4-9
Published in Print: 2010-6-1

© 2010 Versita Warsaw

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Downloaded on 25.2.2024 from
Scroll to top button