Novel genetic and neuropathological insights in neurogenic muscle weakness, ataxia, and retinitis pigmentosa (NARP)

ABSTRACT Introduction: Neurogenic muscle weakness, ataxia, and retinitis pigmentosa (NARP) is caused by m.8993T>G/C mutations in the mitochondrial adenosine triphosphate synthase subunit 6 gene (MT‐ATP6). Traditionally, heteroplasmy levels between 70% and 90% lead to NARP, and >90% result in L...

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Published in:Muscle & nerve 2016-08, Vol.54 (2), p.328-333
Main Authors: Claeys, Kristl G., Abicht, Angela, Häusler, Martin, Kleinle, Stephanie, Wiesmann, Martin, Schulz, Jörg B., Horvath, Rita, Weis, Joachim
Format: Article
Language:English
Subjects:
Adult
Ataxia
Ataxia - complications
Ataxia - genetics
electron microscopy
genetic counseling
Humans
Magnetic Resonance Imaging
Male
MILS
Mitochondria - pathology
Mitochondria - ultrastructure
mitochondrial
Mitochondrial Myopathies - complications
Mitochondrial Myopathies - diagnostic imaging
Mitochondrial Myopathies - genetics
Mitochondrial Proton-Translocating ATPases - genetics
Muscle Weakness - complications
Muscle Weakness - genetics
Mutation
Mutation - genetics
NARP
nerve biopsy
Retinitis Pigmentosa - complications
Retinitis Pigmentosa - diagnostic imaging
Retinitis Pigmentosa - genetics
Sural Nerve - pathology
Sural Nerve - ultrastructure
ultrastructural
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Summary:ABSTRACT Introduction: Neurogenic muscle weakness, ataxia, and retinitis pigmentosa (NARP) is caused by m.8993T>G/C mutations in the mitochondrial adenosine triphosphate synthase subunit 6 gene (MT‐ATP6). Traditionally, heteroplasmy levels between 70% and 90% lead to NARP, and >90% result in Leigh syndrome. Methods: In this study we report a 30‐year‐old man with NARP and m.8993T>G in MT‐ATP6. Results: Although the patient carried the mutation in homoplasmic state in blood with similarly high levels in urine (94%) and buccal swab (92%), he presented with NARP and not the expected, more severe Leigh phenotype. The mutation could not be detected in any of the 3 analyzed tissues of the mother, indicating a large genetic shift between mother and offspring. Nerve biopsy revealed peculiar endoneurial Schwann cell nuclear accumulations, clusters of concentrically arranged Schwann cells devoid of myelinated axons, and degenerated mitochondria. Conclusions: We emphasize the phenotypic variability of the m.8993T>G MT‐ATP6 mutation and the need for caution in predictive counseling in such patients. Muscle Nerve 54: 328–333, 2016
ISSN:0148-639X
1097-4598
DOI:10.1002/mus.25125