Premium
Novel genetic and neuropathological insights in neurogenic muscle weakness, ataxia, and retinitis pigmentosa (NARP)
Author(s) -
Claeys Kristl G.,
Abicht Angela,
Häusler Martin,
Kleinle Stephanie,
Wiesmann Martin,
Schulz Jörg B.,
Horvath Rita,
Weis Joachim
Publication year - 2016
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.25125
Subject(s) - heteroplasmy , retinitis pigmentosa , ataxia , mitochondrial disease , muscle biopsy , mutation , muscle weakness , biology , pathology , endocrinology , medicine , mitochondrial dna , genetics , anatomy , biopsy , neuroscience , gene
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