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

Journal Article · Fri Dec 15 04:00:00 EST 2017 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2017.10.066· OSTI ID:22897522

Mordel, Patrick ^[1]; Schaeffer, Stéphane ^[2]; Dupas, Quentin ^[1]; Laville, Marie-Alice ^[3]; Gérard, Marion ^[4]; Chapon, Françoise ^[2]

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1. Normandie Univ, UNICAEN, CHU Caen, Signalisation, électrophysiologie et imagerie des lésions d'ischémie-reperfusion myocardique, Caen, F-14032 (France)
2. CHU de Caen, Neuromuscular Competence Center, Caen, F-14032 (France)
3. CHU de Caen, Department of ophthalmology, Caen, F-14032 (France)
4. CHU de Caen, Department of medical genetics, Caen, F-14032 (France)

Highlights: • A 2 bp deletion of the ATP6 gene causes a truncated a subunit. • The truncated a subunit is responsible for a decrease of complex V activity. • A 2 bp deletion of the ATP6 gene causes a NARP syndrome. 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.

• OSTI ID: 22897522
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 1-2 Vol. 494; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ATP
BIOSYNTHESIS
BLOOD
DNA
EPILEPSY
ESTERS
FIBROBLASTS
FLUORESCENCE
MITOCHONDRIA
MUSCLES
MUTATIONS
PATIENTS
SENSITIVITY