The heteroplasmic m.14709T&gt;C mutation in the tRNAGlu gene in two Tunisian families with mitochondrial diabetes

Mezghani, Najla; Mkaouar-Rebai, Emna; Mnif, Mouna; Charfi, Nadia; Rekik, Nabila; Youssef, Saoussan; Abid, M.; Fakhfakh, Faiza

doi:10.1016/j.jdiacomp.2009.11.002

Cited by 32 publications

(12 citation statements)

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“…In fact, the m.3243A4G mutation was described associated with hypertrophic cardiomyopathy (Ito et al, 1992;Majamaa-Voltti et al, 2002), and with dilated cardiomyopathy (Tsujita et al, 2008;Vilarinho et al, 1997). In this study, the m.3243A4G is described in the first time associated to dilated cardiomyopathy in Tunisian population when it was previously described only in 1.07% in Tunisian diabetic population (Bouhaha et al, 2010) but it was absent in Tunisian patients with several mitochondrial diseases (Mezghani et al, 2010;Mkaouar-Rebai et al, 2007). The m.3243A4G mutation was detected with high heteroplasmic rate (63.64%) in the blood leucocytes of the studied patient, and it could probably be detected with a higher level in the myocardium.…”

Section: Discussionsupporting

confidence: 49%

Whole mitochondrial genome analysis in two families with dilated mitochondrial cardiomyopathy: detection of mutations in MT-ND2 and MT-TL1 genes

Alila

Rebai

Tabebi

et al. 2015

Mitochondrial DNA Part A

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Pathogenic mitochondrial DNA (mtDNA) mutations leading to mitochondrial dysfunction can cause cardiomyopathy and heart failure. These mutations were described in the mt-tRNA genes and in the mitochondrial protein-coding genes. The aim of this study was to identify the genetic defect in two patients belonging to two families with cardiac dysfunction associated to a wide spectrum of clinical phenotypes. The sequencing analysis of the whole mitochondrial DNA in the two patients and their parents revealed the presence of known polymorphisms associated to cardiomyopathy and two pathogenic mutations in DNA extracted from blood leucocytes: the heteroplasmic m.3243A > G mutation in the MT-TL1 gene in patient A; and the homoplasmic m.5182C > T mutation in the ND2 gene in patient B. Secondary structure analysis of the ND2 protein further supported the deleterious role of the m.5182C > T mutation, as it was found to be involved an extended imbalance in its hydrophobicity and affect its function. In addition, the mitochondrial variants identified in patients A and B classify both of them in the same haplogroup H2a2a1.

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Section: Discussionsupporting

confidence: 49%

Whole mitochondrial genome analysis in two families with dilated mitochondrial cardiomyopathy: detection of mutations in MT-ND2 and MT-TL1 genes

Alila

Rebai

Tabebi

et al. 2015

Mitochondrial DNA Part A

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“…It was indicated that mutations in mtDNA may be associated with obesity. For instance, the tRNA Thr mutation m.10003T>C, as well as the tRNA Glu mutations m.14709T>C, and m.14692A>G have been associated with such disease [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Obesity associated with a novel mitochondrial tRNACys 5802A>G mutation in a Chinese family

et al. 2020

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A Chinese family with matrilineally inherited obesity was assessed and its clinical, genetic, and molecular profiling was conducted. Obesity was observed in matrilineal relatives (3 out of 7) of a single generation (of 3 alive generations) in this family. On pedigree analysis and sequencing of their mitochondrial DNA (mtDNA), a novel homoplasmic mutation of the mitochondrial tRNA Cys gene (5802A>G) was identified in these individuals. This mutation correlated with a destabilized conserved base pair in this tRNA anticodon stem. Position 30 is known to be crucial for carrying out effective codon recognition and stability of tRNA. In accordance with the importance of this conserved site, we observed that the predicted structure of tRNA Cys with the mutation was noticeably remodeled in a molecular dynamics simulation when compared with the isoform of the wild-type. All other 46 mutations observed in the individual's mtDNA were known variants belonging to haplogroup D4. Thus, this is the first report that provides evidence of the association between a mutation in tRNA and an enhanced risk of maternally transmissible obesity, offering more insights into obesity and its underlying nature.

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“…Mitochondria play an imperative role in glucose metabolism, insulin secretion and biogenesis, hence its dysfunction is reportedly found to play a crucial role in diabetes development (Gerbitz et al 1996;Choo Kang et al 2002). Earlier reports showed the association of mitochondrial DNA mutations like 1310C [T, 1382A[C, 1438G[A, 1201A[G, 3243A[G, 3252A[G, 3256A[T, 3264A[C, 3271A[C, 3290T[C, 3303C[T, 3316G[A, 3394T[C, 8296A[G, 8344A[G, 11778G[A, 12026A[G, 12258C[A, 14577T[C, 14709T[C and 16189T[C (Giles et al 1980Alcolado et al 1994;Kalinin et al 1995;Seneca et al 1998;Chinnery et al 2000;Hattori et al 2003;Pranoto 2005;Brandon et al 2005;Liu et al 2007;Mezghani et al 2010;Vijaya Padma et al 2010;Duraisamy et al 2010;Weng et al, 2013) with T2D development. Particularly, mutation in tRNA Leu gene at 3243 (A[G) position and in the subunits of NADH dehydrogenase 1 and 4 have been reported to have strong association with diabetes incidence in different populations (Kalinin et al 1995;Zhao and Zhang 2001;Lam et al 2001;Pranoto 2005;Yu et al 2004;Duraisamy et al 2010;Vijaya Padma et al 2010).…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial ND1 gene mutation analysis in type II diabetes of Karaikudi population

Devi

Elango²,

Ramanan

et al. 2015

Genes Genom

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Mitochondrial single nucleotide polymorphisms (SNPs) are significantly correlated with the development of diabetes mellitus. However, these polymorphisms are emerging to be considerably diverse among different population and regions. Sivaganga district is recently being given importance for genetic studies due to its rigid family structure. Hence, the present study is planned to investigate the correlation between mitochondrial SNP of ND1 gene with type II diabetes (T2D) of Karaikudi population of Sivaganga district. For this study, 206 samples including 105 T2D and 101 healthy volunteers were collected and screened for ND1 gene mutation. Genotyping for the ND1 gene was characterized by polymerase chain reaction, Restriction fragment length polymorphism (RFLP) followed by sequencing. In addition, clinical and biochemical variables were analyzed. RFLP and sequencing results showed G[A transition at 3316 position of ND1 gene in both T2D (6.67 %) and in control subjects (1.9 %). Since the frequency of the mutation was found high in T2D patients, we screened for the mutation in their family members and identified its maternal mode of inheritance. The result warrants for the detailed study to identify population based mitochondrial mutation association with disease development.

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The heteroplasmic m.14709T>C mutation in the tRNAGlu gene in two Tunisian families with mitochondrial diabetes

Cited by 32 publications

References 33 publications

Whole mitochondrial genome analysis in two families with dilated mitochondrial cardiomyopathy: detection of mutations in MT-ND2 and MT-TL1 genes

Whole mitochondrial genome analysis in two families with dilated mitochondrial cardiomyopathy: detection of mutations in MT-ND2 and MT-TL1 genes

Obesity associated with a novel mitochondrial tRNACys 5802A>G mutation in a Chinese family

Mitochondrial ND1 gene mutation analysis in type II diabetes of Karaikudi population

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The heteroplasmic m.14709T>C mutation in the tRNAGlu gene in two Tunisian families with mitochondrial diabetes

Cited by 32 publications

References 33 publications

Whole mitochondrial genome analysis in two families with dilated mitochondrial cardiomyopathy: detection of mutations in MT-ND2 and MT-TL1 genes

Whole mitochondrial genome analysis in two families with dilated mitochondrial cardiomyopathy: detection of mutations in MT-ND2 and MT-TL1 genes

Obesity associated with a novel mitochondrial tRNACys 5802A&gt;G mutation in a Chinese family

Mitochondrial ND1 gene mutation analysis in type II diabetes of Karaikudi population

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Obesity associated with a novel mitochondrial tRNACys 5802A>G mutation in a Chinese family