title: Novel genetic and neuropathological insights in neurogenic muscle weakness, ataxia, and retinitis pigmentosa (NARP).
abstract: 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.
  
  
  
  In this study we report a 30-year-old man with NARP and m.8993T>G in MT-ATP6.
  
  
  
  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.
  
  
  
  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.affiliation: Institute of Neuropathology and Department of Neurology, RWTH Aachen University, Aachen, Germany.|Department of Neurology, University Hospitals Leuven and University of Leuven (KU Leuven), Herestraat 49, 3000, Leuven, Belgium.
authors.forename: Kristl G
authors.initials: KG
authors.lastname: Claeys
authors.affiliation: Medical Genetics Centre, München, Germany.
authors.forename: Angela
authors.initials: A
authors.lastname: Abicht
authors.affiliation: Department of Pediatrics, Division of Neuropediatrics and Social Pediatrics, RWTH Aachen University, Aachen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Häusler
authors.affiliation: Medical Genetics Centre, München, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Kleinle
authors.affiliation: Department of Diagnostic and Interventional Neuroradiology, RWTH Aachen University, Aachen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Wiesmann
authors.affiliation: Department of Neurology and Jülich Aachen Research Alliance-Translational Brain Medicine, RWTH Aachen University, Aachen, Germany.
authors.forename: Jörg B
authors.initials: JB
authors.lastname: Schulz
authors.affiliation: Institute of Genetic Medicine, International Centre for Life, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Rita
authors.initials: R
authors.lastname: Horvath
authors.affiliation: Institute of Neuropathology, RWTH Aachen University, Aachen, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Weis
mesh_terms: D000328:Adult; D001259:Ataxia / Q000150:complications / Q000235:genetics*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008928:Mitochondria / Q000473:pathology / Q000648:ultrastructure; D017240:Mitochondrial Myopathies / Q000150:complications / Q000000981:diagnostic imaging / Q000235:genetics*; D025261:Mitochondrial Proton-Translocating ATPases / Q000235:genetics*; D018908:Muscle Weakness / Q000150:complications / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D012174:Retinitis Pigmentosa / Q000150:complications / Q000000981:diagnostic imaging / Q000235:genetics*; D013497:Sural Nerve / Q000473:pathology / Q000648:ultrastructure
chemical_list: C501005:MT-ATP6 protein, human; D025261:Mitochondrial Proton-Translocating ATPases
keywords: MILS; NARP; electron microscopy; genetic counseling; mitochondrial; nerve biopsy; ultrastructural