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Lookup NU author(s): Dr Krutik Patel, Professor Volker StraubORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2026 The AuthorsNebulin is a large mammalian protein crucial for skeletal muscle sarcomere function. While NEB variants typically cause recessively inherited muscle disorders, a dominantly inherited distal myopathy due to a large multi-exon deletion in NEB was described in 2019 in a single family. We identified 6 unrelated South African families with dominantly inherited distal myopathy associated with a large heterozygous deletion involving exons 14–77 of NEB and collected phenotypic data from 17 affected individuals. The median age at onset was 14 years (range 1 to 48 years), and the phenotype appeared to be mild compared to recessively inherited forms. Distal lower limb onset was most common, and on examination ankle dorsiflexors and toe extensors were the weakest muscle groups in almost all participants. Other frequently involved muscles included finger extensors, flexors, and abductors, and neck flexors. MRI in 3 affected participants showed increased T1 signal intensity in the tibialis anterior muscle, and muscle biopsy (4 participants) revealed non-specific myopathic features. Interestingly, sensory complaints were reported by 7 (41%) participants, but electrodiagnostic abnormalities were heterogeneous and non-specific, and confined to 3 participants from two families. The pathogenic mechanism underlying heterozygous NEB variants remains incompletely understood, and further functional and ultrastructural studies are required.
Author(s): Henning F, Naidu K, Thomas P, Schoeman M, Zaharie D, Patel K, Dominik N, Efthymiou S, Wilson LA, Hanna MG, Straub V, Sagath L, Lehtokari V-L
Publication type: Article
Publication status: Published
Journal: Neuromuscular Disorders
Year: 2026
Volume: 62
Print publication date: 01/05/2026
Online publication date: 21/03/2026
Acceptance date: 21/03/2026
Date deposited: 14/04/2026
ISSN (print): 0960-8966
ISSN (electronic): 1873-2364
Publisher: Elsevier Ltd
URL: https://doi.org/10.1016/j.nmd.2026.106415
DOI: 10.1016/j.nmd.2026.106415
PubMed id: 41886871
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