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A mitochondrial implication in a Tunisian patient with Friedreich's ataxia-like

Maalej, M; Mkaouar-Rebai, E; Mnif, M; Mezghani, N; Ben Ayed, I; Chamkha, I LU ; Abid, M and Fakhfakh, F (2014) In Pathologie et Biologie 62(1). p.8-41
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... (More)

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.

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Contribution to journal
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published
keywords
Adolescent, Consanguinity, DNA Helicases, DNA Mutational Analysis, DNA Replication, DNA, Mitochondrial, DNA-Directed DNA Polymerase, Diagnosis, Differential, Diphtheria-Tetanus-Pertussis Vaccine, Friedreich Ataxia, Haemophilus Vaccines, Humans, Introns, Iron-Binding Proteins, Male, Mitochondrial Diseases, Mitochondrial Proteins, Phenotype, Poliovirus Vaccine, Inactivated, Polymorphism, Genetic, Spinocerebellar Degenerations, Trinucleotide Repeat Expansion, Tunisia, Vaccines, Conjugate
in
Pathologie et Biologie
volume
62
issue
1
pages
8 pages
publisher
Elsevier
external identifiers
  • scopus:84894231669
ISSN
0369-8114
DOI
10.1016/j.patbio.2013.07.013
language
English
LU publication?
no
id
41c94398-02f6-40c6-b3cd-8976af527102
date added to LUP
2016-09-14 12:08:27
date last changed
2017-01-01 08:33:49
@article{41c94398-02f6-40c6-b3cd-8976af527102,
  abstract     = {<p>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&gt;T and the m.16189T&gt;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.</p>},
  author       = {Maalej, M and Mkaouar-Rebai, E and Mnif, M and Mezghani, N and Ben Ayed, I and Chamkha, I and Abid, M and Fakhfakh, F},
  issn         = {0369-8114},
  keyword      = {Adolescent,Consanguinity,DNA Helicases,DNA Mutational Analysis,DNA Replication,DNA, Mitochondrial,DNA-Directed DNA Polymerase,Diagnosis, Differential,Diphtheria-Tetanus-Pertussis Vaccine,Friedreich Ataxia,Haemophilus Vaccines,Humans,Introns,Iron-Binding Proteins,Male,Mitochondrial Diseases,Mitochondrial Proteins,Phenotype,Poliovirus Vaccine, Inactivated,Polymorphism, Genetic,Spinocerebellar Degenerations,Trinucleotide Repeat Expansion,Tunisia,Vaccines, Conjugate},
  language     = {eng},
  number       = {1},
  pages        = {8--41},
  publisher    = {Elsevier},
  series       = {Pathologie et Biologie},
  title        = {A mitochondrial implication in a Tunisian patient with Friedreich's ataxia-like},
  url          = {http://dx.doi.org/10.1016/j.patbio.2013.07.013},
  volume       = {62},
  year         = {2014},
}