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Biochem Biophys Res Commun. 2017 Dec 9;494(1-2):133-137. doi: 10.1016/j.bbrc.2017.10.066. Epub 2017 Oct 18.

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

Author information

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.
5
CHU de Caen, Neuromuscular Competence Center, Caen, F-14032, France; CHU de Caen, Department of Pathology, Caen, F-14032, France.
6
Normandie Univ, UNICAEN, CHU Caen, Signalisation, électrophysiologie et imagerie des lésions d'ischémie-reperfusion myocardique, Caen, F-14032, France; CHU de Caen, Department of biochemistry, Caen, F-14032, France. Electronic address: allouche-s@chu-caen.fr.

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.

KEYWORDS:

ATP6 deletion; Complex V deficiency; Mitochondrial disease; NARP syndrome; Next generation sequencing

PMID:
29054413
DOI:
10.1016/j.bbrc.2017.10.066
[Indexed for MEDLINE]

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