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

Abstract

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.

• Authors: Patrick Mordel, Stéphane Schaeffer, Quentin Dupas, Marie-Alice Laville, Marion Gérard, Françoise Chapon, S Allouche
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 494 Issue 1-2 Pg. 133-137 (12 09 2017) ISSN: 1090-2104 [Electronic] United States
• PMID: 29054413 (Publication Type: Case Reports, Journal Article)
• Copyright: Copyright © 2017 Elsevier Inc. All rights reserved.

Chemical References

• Carrier Proteins
• DNA, Mitochondrial
• MT-ATP6 protein, human
• Membrane Proteins
• Oligomycins
• Adenosine Triphosphate
• Adenosine Triphosphatases
• Mitochondrial Proton-Translocating ATPases
• oligomycin sensitivity-conferring protein

Topics

• Adenosine Triphosphatases (genetics, metabolism)
• Adenosine Triphosphate (metabolism)
• Base Sequence
• Carrier Proteins (genetics, metabolism)
• Cells, Cultured
• DNA Mutational Analysis
• DNA, Mitochondrial (genetics)
• High-Throughput Nucleotide Sequencing
• Humans
• Male
• Membrane Potential, Mitochondrial (drug effects)
• Membrane Proteins (genetics, metabolism)
• Mitochondrial Myopathies (enzymology, genetics)
• Mitochondrial Proton-Translocating ATPases (genetics, metabolism)
• Oligomycins (pharmacology)
• Retinitis Pigmentosa (enzymology, genetics)
• Sequence Deletion
• Syndrome
• Young Adult