title: Co segregation of the m.1555A>G mutation in the MT-RNR1 gene and mutations in MT-ATP6 gene in a family with dilated mitochondrial cardiomyopathy and hearing loss: A whole mitochondrial genome screening.
abstract: Mitochondrial disease refers to a heterogeneous group of disorders resulting in defective cellular energy production due to dysfunction of the mitochondrial respiratory chain, which is responsible for the generation of most cellular energy. Because cardiac muscles are one of the high energy demanding tissues, mitochondrial cardiomyopathies is one of the most frequent mitochondria disorders. Mitochondrial cardiomyopathy has been associated with several point mutations of mtDNA in both genes encoded mitochondrial proteins and mitochondrial tRNA and rRNA. We reported here the first description of mutations in MT-ATP6 gene in two patients with clinical features of dilated mitochondrial cardiomyopathy. The mutational analysis of the whole mitochondrial DNA revealed the presence of m.1555A>G mutation in MT-RNR1 gene associated to the m.8527A>G (p.M>V) and the m.8392C>T (p.136P>S) variations in the mitochondrial MT-ATP6 gene in patient1 and his family members with variable phenotype including hearing impairment. The second patient with isolated mitochondrial cardiomyopathy presented the m.8605C>T (p.27P>S) mutation in the MT-ATP6 gene. The three mutations p.M1V, p.P27S and p.P136S detected in MT-ATP6 affected well conserved residues of the mitochondrial protein ATPase 6. In addition, the substitution of proline residue at position 27 and 136 effect hydrophobicity and structure flexibility conformation of the protein.
authors.affiliation: Laboratoire de Génétique Moléculaire et Fonctionnelle, Faculté des Sciences de Sfax, University of Sfax, Tunisia. Electronic address: alilafersiolfa@yahoo.fr.
authors.forename: Olfa
authors.initials: O
authors.lastname: Alila-Fersi
authors.affiliation: Department of Mitochondrial Medicine, Lund University, Sweden.
authors.forename: Imen
authors.initials: I
authors.lastname: Chamkha
authors.affiliation: Service de Réanimation Pédiatrique, C.H.U. Hédi Chaker de Sfax, Tunisia.
authors.forename: Imen
authors.initials: I
authors.lastname: Majdoub
authors.affiliation: Service de Réanimation Pédiatrique, C.H.U. Hédi Chaker de Sfax, Tunisia.
authors.forename: Lamia
authors.initials: L
authors.lastname: Gargouri
authors.affiliation: Laboratoire de Génétique Moléculaire et Fonctionnelle, Faculté des Sciences de Sfax, University of Sfax, Tunisia.
authors.forename: Emna
authors.initials: E
authors.lastname: Mkaouar-Rebai
authors.affiliation: Laboratoire de Génétique Moléculaire Humaine, Faculté de Médecine de Sfax, University of Sfax, Tunisia.
authors.forename: Mouna
authors.initials: M
authors.lastname: Tabebi
authors.affiliation: Department of Applied Biology, College of Sciences, University of Sharjah, Sharjah, United Arab Emirates.
authors.forename: Abdelaziz
authors.initials: A
authors.lastname: Tlili
authors.affiliation: Laboratoire de Génétique Moléculaire Humaine, Faculté de Médecine de Sfax, University of Sfax, Tunisia.
authors.forename: Leila
authors.initials: L
authors.lastname: Keskes
authors.affiliation: Service de Réanimation Pédiatrique, C.H.U. Hédi Chaker de Sfax, Tunisia.
authors.forename: Abdelmajid
authors.initials: A
authors.lastname: Mahfoudh
authors.affiliation: Laboratoire de Génétique Moléculaire et Fonctionnelle, Faculté des Sciences de Sfax, University of Sfax, Tunisia. Electronic address: faiza.fakhfakh02@gmail.com.
authors.forename: Faiza
authors.initials: F
authors.lastname: Fakhfakh
mesh_terms: D000293:Adolescent; D000595:Amino Acid Sequence; D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000235:genetics*; D054629:Genome, Mitochondrial; D034381:Hearing Loss / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D008929:Mitochondria, Heart / Q000235:genetics*; D025261:Mitochondrial Proton-Translocating ATPases / Q000235:genetics*; D009154:Mutation; D012335:RNA, Ribosomal / Q000235:genetics*; D017386:Sequence Homology, Amino Acid
chemical_list: C501005:MT-ATP6 protein, human; D012335:RNA, Ribosomal; C075526:RNA, ribosomal, 12S; D025261:Mitochondrial Proton-Translocating ATPases
keywords: Dilated mitochondrial cardiomyopathy; Hearing loss; m.1555A>G; m.8527A>G; m.8605C>T; m.8932C>T