title: Whole mitochondrial genome analysis in two families with dilated mitochondrial cardiomyopathy: detection of mutations in MT-ND2 and MT-TL1 genes.
abstract: 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.
authors.affiliation: a Laboratoire de Génétique Moléculaire Humaine, Faculté de Médecine de Sfax , Sfax , Tunisia .
authors.forename: Olfa Fersi
authors.initials: OF
authors.lastname: Alila
authors.affiliation: a Laboratoire de Génétique Moléculaire Humaine, Faculté de Médecine de Sfax , Sfax , Tunisia .
authors.forename: Emna Mkaouar
authors.initials: EM
authors.lastname: Rebai
authors.affiliation: a Laboratoire de Génétique Moléculaire Humaine, Faculté de Médecine de Sfax , Sfax , Tunisia .
authors.forename: Mouna
authors.initials: M
authors.lastname: Tabebi
authors.affiliation: b Service de Pédiatrie, C.H.U. Farhat Hached de Sousse , Sousse , Tunisia , and.
authors.forename: Amel
authors.initials: A
authors.lastname: Tej
authors.affiliation: a Laboratoire de Génétique Moléculaire Humaine, Faculté de Médecine de Sfax , Sfax , Tunisia .
authors.forename: Imen
authors.initials: I
authors.lastname: Chamkha
authors.affiliation: c Department of Applied Biology , College of Sciences, University of Sharjah , Sharjah , UAE.
authors.forename: Abdelaziz
authors.initials: A
authors.lastname: Tlili
authors.affiliation: b Service de Pédiatrie, C.H.U. Farhat Hached de Sousse , Sousse , Tunisia , and.
authors.forename: Jihene
authors.initials: J
authors.lastname: Bouguila
authors.affiliation: b Service de Pédiatrie, C.H.U. Farhat Hached de Sousse , Sousse , Tunisia , and.
authors.forename: Samia
authors.initials: S
authors.lastname: Tilouche
authors.affiliation: b Service de Pédiatrie, C.H.U. Farhat Hached de Sousse , Sousse , Tunisia , and.
authors.forename: Nejla
authors.initials: N
authors.lastname: Soyah
authors.affiliation: b Service de Pédiatrie, C.H.U. Farhat Hached de Sousse , Sousse , Tunisia , and.
authors.forename: Lamia
authors.initials: L
authors.lastname: Boughamoura
authors.affiliation: a Laboratoire de Génétique Moléculaire Humaine, Faculté de Médecine de Sfax , Sfax , Tunisia .
authors.forename: Faiza
authors.initials: F
authors.lastname: Fakhfakh
mesh_terms: D009202:Cardiomyopathies / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000235:genetics; D005260:Female; D054629:Genome, Mitochondrial / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics; D009245:NADH Dehydrogenase / Q000235:genetics*; D010802:Phylogeny; D012356:RNA, Transfer, Leu / Q000235:genetics*
chemical_list: D004272:DNA, Mitochondrial; C000625432:MT-TL1 tRNA, human; D012356:RNA, Transfer, Leu; D009245:NADH Dehydrogenase; C521326:NADH dehydrogenase subunit 2, human
keywords: MT-TL1 gene; Mitochondrial cardiomyopathy; ND2 gene; m.3243A > G; m.5182C > T