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 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.

• Authors: Kristl G Claeys, Angela Abicht, Martin Häusler, Stephanie Kleinle, Martin Wiesmann, Jörg B Schulz, Rita Horvath, Joachim Weis
• Journal: Muscle & nerve (Muscle Nerve) Vol. 54 Issue 2 Pg. 328-33 (08 2016) ISSN: 1097-4598 [Electronic] United States
• PMID: 27015314 (Publication Type: Case Reports, Journal Article)
• Copyright: © 2016 Wiley Periodicals, Inc.

Chemical References

• MT-ATP6 protein, human
• Mitochondrial Proton-Translocating ATPases

Topics

• Adult
• Ataxia (complications, genetics)
• Humans
• Magnetic Resonance Imaging
• Male
• Mitochondria (pathology, ultrastructure)
• Mitochondrial Myopathies (complications, diagnostic imaging, genetics)
• Mitochondrial Proton-Translocating ATPases (genetics)
• Muscle Weakness (complications, genetics)
• Mutation (genetics)
• Retinitis Pigmentosa (complications, diagnostic imaging, genetics)
• Sural Nerve (pathology, ultrastructure)