Nowa wersja platformy, zawierająca wyłącznie zasoby pełnotekstowe, jest już dostępna.
Przejdź na


Preferencje help
Widoczny [Schowaj] Abstrakt
Liczba wyników
2010 | 5 | 3 | 322-328
Tytuł artykułu

Analysis of mtDNA A3243G mutation frequency in Hungary

Treść / Zawartość
Warianty tytułu
Języki publikacji
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.
Słowa kluczowe

Opis fizyczny
  • Department of Neurology, Centre for Molecular Neurology, Semmelweis University, 1083, Budapest, Hungary
  • Department of Medical Genetics, University of Pécs, 7624, Pécs, Hungary
  • Department of Medical Genetics, University of Pécs, 7624, Pécs, Hungary
  • Department of Neurology, Centre for Molecular Neurology, Semmelweis University, 1083, Budapest, Hungary
  • Department of Neurology, Centre for Molecular Neurology, Semmelweis University, 1083, Budapest, Hungary
  • National Stroke Center, National Institute of Neurosurgery, 1145, Budapest, Hungary
  • Department of Neurology, Borsod - Abaúj - Zemplén County Hospital, 3526, Miskolc, Hungary
  • Department of Neurology, Jósa András County Hospital, 4400, Nyíregyháza, Hungary
  • Department of Neurology, Centre for Molecular Neurology, Semmelweis University, 1083, Budapest, Hungary
  • Department of Medical Genetics, University of Pécs, 7624, Pécs, Hungary
  • Department of Neurology, Centre for Molecular Neurology, Semmelweis University, 1083, Budapest, Hungary,
  • [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[Crossref]
  • [2] Finsterer J., Genetic, pathogenetic, and phenotypic implications of the mitochondrial A3243G tRNALeu(UUR) mutation, Acta Neurol Scand., 2007, 116, 1–14[Crossref][WoS]
  • [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[Crossref]
  • [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[Crossref]
  • [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[Crossref]
  • [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
  • [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[Crossref][WoS]
  • [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[Crossref][WoS]
  • [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[Crossref]
  • [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[Crossref]
  • [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[Crossref]
  • [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[Crossref]
  • [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
  • [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[Crossref]
  • [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 [WoS]
  • [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
  • [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[Crossref]
  • [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
  • [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[WoS][Crossref]
  • [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
  • [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
  • [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[Crossref]
  • [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[Crossref]
  • [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
  • [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
  • [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[Crossref]
  • [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[Crossref]
  • [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
  • [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
  • [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
  • [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[Crossref]
  • [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[Crossref]
  • [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[Crossref]
  • [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[Crossref]
  • [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
Typ dokumentu
Identyfikator YADDA
JavaScript jest wyłączony w Twojej przeglądarce internetowej. Włącz go, a następnie odśwież stronę, aby móc w pełni z niej korzystać.