Dominantly inherited distal nemaline/cap myopathy caused by a large deletion in the nebulin gene.

Autor: Kiiski KJ; The Folkhälsan Research Center, Helsinki, Finland and Medicum, University of Helsinki, Helsinki, Finland., Lehtokari VL; The Folkhälsan Research Center, Helsinki, Finland and Medicum, University of Helsinki, Helsinki, Finland. Electronic address: vilma.lehtokari@helsinki.fi., Vihola AK; The Folkhälsan Research Center, Helsinki, Finland and Medicum, University of Helsinki, Helsinki, Finland., Laitila JM; The Folkhälsan Research Center, Helsinki, Finland and Medicum, University of Helsinki, Helsinki, Finland., Huovinen S; Department of Pathology, Tampere University Hospital, Fimlab Laboratories, Tampere, Finland., Sagath LJ; The Folkhälsan Research Center, Helsinki, Finland and Medicum, University of Helsinki, Helsinki, Finland., Evilä AE; The Folkhälsan Research Center, Helsinki, Finland and Medicum, University of Helsinki, Helsinki, Finland., Paetau AE; Department of Pathology, HUSLAB, Helsinki University Hospital & University of Helsinki, Finland., Sewry CA; Dubowitz Neuromuscular Centre, UCL Institute of Child Health and Great Ormond Street Hospital, London, UK., Hackman PB; The Folkhälsan Research Center, Helsinki, Finland and Medicum, University of Helsinki, Helsinki, Finland., Pelin KB; The Folkhälsan Research Center, Helsinki, Finland and Medicum, University of Helsinki, Helsinki, Finland; Molecular and Integrative Biosciences Research Programme, Faculty of Biological and Environmental Sciences, University of Helsinki, Helsinki, Finland., Wallgren-Pettersson C; The Folkhälsan Research Center, Helsinki, Finland and Medicum, University of Helsinki, Helsinki, Finland., Udd B; The Folkhälsan Research Center, Helsinki, Finland and Medicum, University of Helsinki, Helsinki, Finland; Neuromuscular Research Center, Tampere University and University Hospital, Tampere, Finland; Department of Neurology, Vaasa Central Hospital, Vaasa, Finland.
Jazyk: angličtina
Zdroj: Neuromuscular disorders : NMD [Neuromuscul Disord] 2019 Feb; Vol. 29 (2), pp. 97-107. Date of Electronic Publication: 2018 Dec 20.
DOI: 10.1016/j.nmd.2018.12.007
Abstrakt: We report the first family with a dominantly inherited mutation of the nebulin gene (NEB). This ∼100 kb in-frame deletion encompasses NEB exons 14-89, causing distal nemaline/cap myopathy in a three-generation family. It is the largest deletion characterized in NEB hitherto. The mutated allele was shown to be expressed at the mRNA level and furthermore, for the first time, a deletion was shown to cause the production of a smaller mutant nebulin protein. Thus, we suggest that this novel mutant nebulin protein has a dominant-negative effect, explaining the first documented dominant inheritance of nebulin-caused myopathy. The index patient, a young man, was more severely affected than his mother and grandmother. His first symptom was foot drop at the age of three, followed by distal muscle atrophy, slight hypomimia, high-arched palate, and weakness of the neck and elbow flexors, hands, tibialis anterior and toe extensors. Muscle biopsies showed myopathic features with type 1 fibre predominance in the index patient and nemaline bodies and cap-like structures in biopsies from his mother and grandmother. The muscle biopsy findings constitute a further example of nemaline bodies and cap-like structures being part of the same spectrum of pathological changes.
(Copyright © 2019 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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