Congenital asymmetric distal myopathy with hemifacial weakness caused by a heterozygous large de novo mosaic deletion in nebulin
| Autor: | Katarina Pelin, K. Kiiski, Manu Jokela, Maria Gardberg, Peter Hackman, Salla Välipakka, L. Sagath, Vilma Lotta Lehtokari, Anna Vihola, Bjarne Udd, Carina Wallgren-Pettersson |
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| Přispěvatelé: | Medicum, Department of Medical and Clinical Genetics, Faculty of Biological and Environmental Sciences, University of Helsinki, Katarina Pelin / Principal Investigator, Molecular and Integrative Biosciences Research Programme, Biosciences, Genetics, HUS Diagnostic Center, HUSLAB |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty COPY-NUMBER VARIATION CORE-ROD MYOPATHY 03 medical and health sciences Nebulin Exon 0302 clinical medicine Nemaline myopathy medicine Copy-number variation Myopathy Nemaline bodies Genetics (clinical) biology Mosaicism Copy number variation MUTATIONS 3112 Neurosciences Muscle weakness NEMALINE MYOPATHY MUSCLE medicine.disease Congenital myopathy GENE de novo mutation Large deletion 030104 developmental biology Neurology Pediatrics Perinatology and Child Health biology.protein Neurology (clinical) medicine.symptom 030217 neurology & neurosurgery |
| Popis: | We report the first mosaic mutation, a deletion of exons 11-107, identified in the nebulin gene in a Finnish patient presenting with a predominantly distal congenital myopathy and asymmetric muscle weakness. The female patient is ambulant and currently 26 years old. Muscle biopsies showed myopathic features with type 1 fibre predominance, strikingly hypotrophic type 2 fibres and central nuclei, but no nemaline bodies. The deletion was detected in a copy number variation analysis based on next-generation sequencing data. The parents of the patient did not carry the deletion. Mosaicism was detected using a custom, targeted comparative genomic hybridisation array. Expression of the truncated allele, less than half the size of full-length nebulin, was confirmed by Western blotting. The clinical and histological picture resembled that of a family with a slightly smaller deletion, and that in patients with recessively inherited distal forms of nebulin-caused myopathy. Asymmetry, however, was a novel feature. (c) 2021 Elsevier B.V. All rights reserved. |
| Databáze: | OpenAIRE |
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