title: A mitochondrial implication in a Tunisian patient with Friedreich's ataxia-like.
abstract: Genes encoding the DNA helicase TWINKLE (C10orf2) or the two subunits of mtDNA polymerase γ (POLγ) (POLG1 and POLG2) have a direct effect on the mitochondrial DNA replication machinery and were reported in many mitochondrial disorders. Friedreich's ataxia (FRDA) is the common cause of ataxia often associated with the expansion of a GAA repeat in intron 1 of the frataxin gene (FXN). Mitochondrial DNA could be considered as a candidate modiﬁer factor for FRDA disease, since mitochondrial oxidative stress is thought to be involved in the pathogenesis of this disease. We screened the FXN, POLG1 and C10orf2 genes in a Tunisian patient with clinical features of Friedreich's ataxia-like. The results showed the absence of the expansion of a GAA triplet repeat in intron 1 of the FXN gene. Besides, the sequencing of all the exons and their flanking regions of the FXN, POLG1 and C10orf2 genes revealed the presence of intronic polymorphisms. In addition, screening of the mtDNA revealed the presence of several mitochondrial known variations and the absence of mitochondrial deletions in this patient. The detected m.16187C>T and the m.16189T>C change the order of the homopolymeric tract of cytosines between 16184 and 16193 in the mitochondrial D-loop and could lead to a mitochondrial dysfunction by inhibiting replication and affecting protein involved in the replication process of the mtDNA which could be responsible for the clinical features of Friedreich ataxia observed in the studied patient.
authors.affiliation: Laboratoire de génétique moléculaire humaine, faculté de médecine de Sfax, avenue Magida Boulila, 3029 Sfax, Tunisia.
authors.forename: M
authors.initials: M
authors.lastname: Maalej
authors.affiliation: Laboratoire de génétique moléculaire humaine, faculté de médecine de Sfax, avenue Magida Boulila, 3029 Sfax, Tunisia. Electronic address: emna_mkaouar@mail2world.com.
authors.forename: E
authors.initials: E
authors.lastname: Mkaouar-Rebai
authors.affiliation: Service d'endocrinologie, CHU Hédi Chaker de Sfax, avenue Magida Boulila, 3029 Sfax, Tunisia.
authors.forename: M
authors.initials: M
authors.lastname: Mnif
authors.affiliation: Laboratoire de génétique moléculaire humaine, faculté de médecine de Sfax, avenue Magida Boulila, 3029 Sfax, Tunisia.
authors.forename: N
authors.initials: N
authors.lastname: Mezghani
authors.affiliation: Laboratoire de génétique moléculaire humaine, faculté de médecine de Sfax, avenue Magida Boulila, 3029 Sfax, Tunisia.
authors.forename: I
authors.initials: I
authors.lastname: Ben Ayed
authors.affiliation: Laboratoire de génétique moléculaire humaine, faculté de médecine de Sfax, avenue Magida Boulila, 3029 Sfax, Tunisia.
authors.forename: I
authors.initials: I
authors.lastname: Chamkha
authors.affiliation: Service d'endocrinologie, CHU Hédi Chaker de Sfax, avenue Magida Boulila, 3029 Sfax, Tunisia.
authors.forename: M
authors.initials: M
authors.lastname: Abid
authors.affiliation: Laboratoire de génétique moléculaire humaine, faculté de médecine de Sfax, avenue Magida Boulila, 3029 Sfax, Tunisia.
authors.forename: F
authors.initials: F
authors.lastname: Fakhfakh
mesh_terms: D000293:Adolescent; D003241:Consanguinity; D004265:DNA Helicases / Q000235:genetics; D004252:DNA Mutational Analysis; D000074002:DNA Polymerase gamma; D004261:DNA Replication; D004272:DNA, Mitochondrial / Q000235:genetics*; D004259:DNA-Directed DNA Polymerase / Q000235:genetics; D003937:Diagnosis, Differential; D015721:Diphtheria-Tetanus-Pertussis Vaccine; D005621:Friedreich Ataxia / Q000175:diagnosis / Q000235:genetics; D018073:Haemophilus Vaccines; D006801:Humans; D007438:Introns; D033862:Iron-Binding Proteins / Q000235:genetics; D008297:Male; D028361:Mitochondrial Diseases / Q000145:classification / Q000175:diagnosis / Q000235:genetics*; D024101:Mitochondrial Proteins / Q000235:genetics; D010641:Phenotype; D011054:Poliovirus Vaccine, Inactivated; D011110:Polymorphism, Genetic; D013132:Spinocerebellar Degenerations / Q000145:classification / Q000175:diagnosis / Q000235:genetics*; D019680:Trinucleotide Repeat Expansion; D014416:Tunisia; D018074:Vaccines, Conjugate; D000096923:Frataxin
chemical_list: D004265:DNA Helicases; D000074002:DNA Polymerase gamma; D004272:DNA, Mitochondrial; D004259:DNA-Directed DNA Polymerase; D015721:Diphtheria-Tetanus-Pertussis Vaccine; D018073:Haemophilus Vaccines; D033862:Iron-Binding Proteins; D024101:Mitochondrial Proteins; D011054:Poliovirus Vaccine, Inactivated; D018074:Vaccines, Conjugate; D000096923:Frataxin; C541234:diphtheria-tetanus-five component acellular pertussis-inactivated poliomyelitis -Haemophilus influenzae type b conjugate vaccine; C413027:POLG protein, human; C431576:TWNK protein, human
keywords: ADNmt; Ataxie de Friedreich; C10orf2; D-Loop; FXN; Friedreich's ataxia; MT-DLoop; POLG1; Twinkle; mtDNA