Molecular genetic analysis of the m.A3243G mutation of the tRNALeu (UUR) gene in a population of Moroccan deaf diabetics

Taha Rhouda, Fatima Zahra Kehailou, Fatima Zahra EL Mskini, Ali Labriji, Mohammed Jabari, Houriya Mestaghanmi


Background: The mitochondrial DNA (mtDNA) m.A3243G mutation of the tRNALeu (UUR) gene presents clinically heterogeneous phenotypes and is often responsible for diabetes, with or without deafness syndrome. The aim of this study was to search for this pathogenic mutation in 3 diabetics with bilateral deafness and a family history of diabetes.

Methods: mtDNA was extracted from the patients' whole blood. After PCR amplification, the DNA was sequenced and analyzed.

Results: The sequencing results showed the absence of the most common mtDNA mutation m.A3243G in diabetic families with individuals who suffer from hearing loss.

Conclusions: The m.A3243G mutation in the mitochondrial tRNALeu (UUR) Leu gene was not found to be a common cause of type 2 diabetes and deafness. These results suggest that there may be genetic causes for this phenotype.

Keywords: Diabetes; Deafness; M.A3243G Mutation; Mitochondrial DNA 

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Bouatia-Naji N, Bonnefond A, Froguel P. Inputs from the genetics of fasting glucose: lessons for diabetes. Medical Sciences (Paris), (2009); 25(11): 897-902.

Schaefer AM, Walker M, Turnbull DM, Taylor RW. Endocrine disorders in mitochondrial disease. Molecular and Cellular Endocrinology, (2013); 379(1-2): 2-11.

van den Ouweland JM, Lemkes HH, Ruitenbeek W, Sandkuijl LA, de Vijlder MF, et al. Mutation in mitochondrial tRNA(Leu)(UUR) gene in a large pedigree with maternally transmitted type II diabetes mellitus and deafness. Nature Genetics, (1992); 1(5): 368-371.

Murphy R, Turnbull DM, Walker M, Hattersley AT. Clinical features, diagnosis and management of maternally inherited diabetes and deafness (MIDD) associated with the 3243A>G mitochondrial point mutation. Diabetic Medicine, (2008); 25(4): 383-399.

Goto Y, Nonaka I, Horai S. A mutation in the tRNA(Leu)(UUR) gene associated with the MELAS subgroup of mitochondrial encephalomyopathies. Nature, (1990); 348(6302): 651-653.

Wallace DC. A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: a dawn for evolutionary medicine. Annual Review of Genetics, (2005); 39359-407.

van den Ouweland JM, Lemkes HH, Trembath RC, Ross R, Velho G, et al. Maternally inherited diabetes and deafness is a distinct subtype of diabetes and associates with a single point mutation in the mitochondrial tRNA(Leu(UUR)) gene. Diabetes, (1994); 43(6): 746-751.

Biousse V, Brown MD, Newman NJ, Allen JC, Rosenfeld J, et al. De novo 14484 mitochondrial DNA mutation in monozygotic twins discordant for Leber's hereditary optic neuropathy. Neurology, (1997); 49(4): 1136-1138.

Yamamoto M. Did de novo MELAS common mitochondrial DNA point mutation (mtDNA 3243, A–>G transition) occur in the mother of a proband of a Japanese MELAS pedigree? Journal of the Neurological Sciences, (1996); 135(1): 81-84.

Jiang Z, Zhang Y, Yan J, Li F, Geng X, et al. De Novo Mutation of m.3243A>G together with m.16093T>C Associated with Atypical Clinical Features in a Pedigree with MIDD Syndrome. Journal of Diabetes Research, (2019); 20195184647.

Laloi-Michelin M, Meas T, Ambonville C, Bellanné-Chantelot C, Beaufils S, et al. The clinical variability of maternally inherited diabetes and deafness is associated with the degree of heteroplasmy in blood leukocytes. The Journal of Clinical Endocrinology & Metabolism, (2009); 94(8): 3025-3030.

Ohkubo K, Yamano A, Nagashima M, Mori Y, Anzai K, et al. Mitochondrial Gene Mutations in the tRNALeu(UUR) Region and Diabetes: Prevalence and Clinical Phenotypes in Japan. Clinical Chemistry, (2001); 47(9): 1641-1648.

Corona P, Antozzi C, Carrara F, D'Incerti L, Lamantea E, et al. A novel mtDNA mutation in the ND5 subunit of complex I in two MELAS patients. Annals of Neurology, (2001); 49(1): 106-110.

Bindoff LA, Engelsen BA. Mitochondrial diseases and epilepsy. Epilepsia, (2012); 53 Suppl 492-97.

Tabebi M, Mkaouar-Rebai E, Mnif M, Kallabi F, Ben Mahmoud A, et al. A novel mutation MT-COIII m.9267G>C and MT-COI m.5913G>A mutation in mitochondrial genes in a Tunisian family with maternally inherited diabetes and deafness (MIDD) associated with severe nephropathy. Biochemical and Biophysical Research Communications, (2015); 459(3): 353-360.

Jardel C, Rucheton B. Diagnostic des maladies mitochondriales. Revue Francophone des Laboratoires, (2018); 2018(501): 36-48.

McFarland R, Taylor RW, Turnbull DM. A neurological perspective on mitochondrial disease. The Lancet Neurology, (2010); 9(8): 829-840.

Auré K, Jardel C, Lombès A. [Mitochondrial diseases: molecular mechanisms, clinical presentations and diagnosis investigations]. Annales de Pathologie, (2005); 25(4): 270-281.

Auré K, Ogier de Baulny H, Laforêt P, Jardel C, Eymard B, et al. Chronic progressive ophthalmoplegia with large-scale mtDNA rearrangement: can we predict progression? Brain, (2007); 130(Pt 6): 1516-1524.

Alonso L (2016) Déficits de la chaîne respiratoire mitochondriale avec instabilité de Œ ADN mitochondrial : identification de nouveaux gènes et mécanismes: Université Côte d’Azur, 2016. Français. ffNNT : 2016AZUR4101ff. fftel-01466739f. 132 p.

Gerbitz KD, van den Ouweland JM, Maassen JA, Jaksch M. Mitochondrial diabetes mellitus: a review. Biochimica et Biophysica Acta, (1995); 1271(1): 253-260.

Hsouna S, Ben Halim N, Lasram K, Arfa I, Jamoussi H, et al. Association study of mitochondrial DNA polymorphisms with type 2 diabetes in Tunisian population. Mitochondrial DNA, (2015); 26(3): 367-372.

Abrar S, Muhammad K, Zaman H, Khan S, Nouroz F, et al. Molecular genetic analysis of Type II diabetes associated m.3243A>G mitochondrial DNA mutation in a Pakistani family. Egyptian Journal of Medical Human Genetics, (2017); 18(3): 305-308.

Zambelli A, Vidal-Rioja L. Lack of association between mitochondrial DNA mutation np3243 and maternally inherited diabetes mellitus. Clinical Biochemistry, (1999); 32(1): 81-82.

Mkaouar-Rebai E, Tlili A, Masmoudi S, Belguith N, Charfeddine I, et al. Mutational analysis of the mitochondrial tRNALeu(UUR) gene in Tunisian patients with mitochondrial diseases. Biochemical and Biophysical Research Communications, (2007); 355(4): 1031-1037.

Bouhaha R, Abid Kamoun H, Elgaaied A, Ennafaa H. A3243G mitochondrial DNA mutation in Tunisian diabetic population. Tunisie Medicale, (2010); 88(9): 642-645.

Ishak AR, Puspitaningrum R, Utari RD, Ferania M, Adhiyanto C, et al. Mutation of mtDNA ND1 Gene in 20 Type 2 Diabetes Mellitus Patients of Gorontalonese and Javanese Ethnicity. HAYATI Journal of Biosciences, (2014); 21(4): 159-165.

Khan N, Ullah H, Raziq A, Khan A, Khan M. Molecular genetic analysis of leucine tRNA in relevance to type 2 diabetes mellitus. Clinical Diabetology, (2020); 9(3): 167-173.

Yorifuji T, Fujimaru R, Hosokawa Y, Tamagawa N, Shiozaki M, et al. Comprehensive molecular analysis of Japanese patients with pediatric-onset MODY-type diabetes mellitus. Pediatric Diabetes, (2012); 13(1): 26-32.

FawziO A, Za H, AbdelKawyS I, Al-DiwanyO I, Adela M, et al. Mitochondrial Mutation In Egyptian Patients With Type 2 Diabetes Mellitus. The Egyptian Journal of Hospital Medicine, (2006); 23245-256.

Liao WQ, Pang Y, Yu CA, Wen JY, Zhang YG, et al. Novel mutations of mitochondrial DNA associated with type 2 diabetes in Chinese Han population. The Tohoku Journal of Experimental Medicine, (2008); 215(4): 377-384.


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