A 2 bp deletion in the mitochondrial ATP 6 gene responsible for the NARP (neuropathy, ataxia, and retinitis pigmentosa) syndrome

Autor: Stéphane Schaeffer, Marie-Alice Laville, Patrick Mordel, Françoise Chapon, Quentin Dupas, Stéphane Allouche, Marion Gérard
Přispěvatelé: Signalisation, électrophysiologie et imagerie des lésions d’ischémie-reperfusion myocardique (SEILIRM), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Centre de compétences pathologies neuromusculaires [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service d'ophtalmologie [CHU Caen], Université de Lorraine (UL), Hôpital Côte de Nacre [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Mobilités : Vieillissement, Pathologie, Santé (COMETE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Caen Normandie (UNICAEN), Service de biochimie [CHU Caen]
Rok vydání: 2017
Předmět:
Male
0301 basic medicine
[SDV]Life Sciences [q-bio]
DNA Mutational Analysis
[SHS.PSY]Humanities and Social Sciences/Psychology
Biochemistry
Adenosine Triphosphate
0302 clinical medicine
Mitochondrial myopathy
Cells
Cultured
Sequence Deletion
ATP6 deletion
Adenosine Triphosphatases
Membrane Potential
Mitochondrial
Genetics
High-Throughput Nucleotide Sequencing
Mitochondrial Myopathies
Syndrome
Mitochondrial Proton-Translocating ATPases
Heteroplasmy
3. Good health
medicine.symptom
Retinitis Pigmentosa
Ataxia
Mitochondrial disease
Biophysics
Biology
DNA
Mitochondrial
Young Adult
03 medical and health sciences
Complex V deficiency
Next generation sequencing
Retinitis pigmentosa
medicine
Humans
Molecular Biology
Base Sequence
Neuropathy
ataxia
and retinitis pigmentosa
[SCCO.NEUR]Cognitive science/Neuroscience
Membrane Proteins
Muscle weakness
Cell Biology
medicine.disease
Molecular biology
030104 developmental biology
Myoclonic epilepsy
Oligomycins
NARP syndrome
Carrier Proteins
030217 neurology & neurosurgery
Zdroj: Biochemical and Biophysical Research Communications
Biochemical and Biophysical Research Communications, Elsevier, 2017, 494 (1-2), pp.133-137. ⟨10.1016/j.bbrc.2017.10.066⟩
ISSN: 0006-291X
1090-2104
Popis: International audience; Mitochondrial (mt) DNA-associated NARP (neurogenic muscle weakness, ataxia, and retinitis pigmentosa) syndrome is due to mutation in the MT-ATP6 gene. We report the case of a 18-year-old man who presented with deafness, a myoclonic epilepsy, muscle weakness since the age of 10 and further developed a retinitis pigmentosa and ataxia. The whole mtDNA analysis by next-generation sequencing revealed the presence of the 2 bp microdeletion m.9127-9128 del AT in the ATP6 gene at 82% heteroplasmy in muscle and to a lower load in blood (10-20%) and fibroblasts (50%). Using the patient's fibroblasts, we demonstrated a 60% reduction of the oligomycin-sensitive ATPase hydrolytic activity, a 40% decrease in the ATP synthesis and determination of the mitochondrial membrane potential using the fluorescent probe tetramethylrhodamine, ethyl ester indicated a significant reduction in oligomycin sensitivity. In conclusion, we demonstrated that this novel AT deletion in the ATP6 gene is pathogenic and responsible for the NARP syndrome.
Databáze: OpenAIRE
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