Intrafamilial phenotypic heterogeneity related to a new DMD splice site variant.

Autor: Coimbra Neto AR; Department of Neurology, School of Medical Sciences, University of Campinas (UNICAMP), 126. Cidade Universitaria 'Zeferino Vaz', Campinas, SP 13083-887, Brazil., de Carvalho SC; Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, SP, Brazil; Postgraduate Program in Biomedical Science, University Centre of the Hermínio Ometto Foundation, Araras, SP, Brazil., Leoni TB; Department of Neurology, School of Medical Sciences, University of Campinas (UNICAMP), 126. Cidade Universitaria 'Zeferino Vaz', Campinas, SP 13083-887, Brazil., Iwabe C; Department of Neurology, School of Medical Sciences, University of Campinas (UNICAMP), 126. Cidade Universitaria 'Zeferino Vaz', Campinas, SP 13083-887, Brazil., Silva TQAC; Department of Internal Medicine, Discipline of Cardiology, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, Brazil., Coelho-Filho OR; Department of Internal Medicine, Discipline of Cardiology, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, Brazil., Marques MJ; Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, SP, Brazil., Nucci A; Department of Neurology, School of Medical Sciences, University of Campinas (UNICAMP), 126. Cidade Universitaria 'Zeferino Vaz', Campinas, SP 13083-887, Brazil., França MC Jr; Department of Neurology, School of Medical Sciences, University of Campinas (UNICAMP), 126. Cidade Universitaria 'Zeferino Vaz', Campinas, SP 13083-887, Brazil. Electronic address: mcfjr@unicamp.br.
Jazyk: angličtina
Zdroj: Neuromuscular disorders : NMD [Neuromuscul Disord] 2021 Aug; Vol. 31 (8), pp. 788-797. Date of Electronic Publication: 2021 Jun 02.
DOI: 10.1016/j.nmd.2021.05.013
Abstrakt: Dystrophinopathies are a group of X-linked neuromuscular disorders that result from pathogenic variants in the DMD gene. Their pathophysiological substrate is the defective expression of dystrophin in many tissues. While patients from the same pedigree usually present similar dystrophin expression and clinical course, the extent of cardiac and skeletal muscle involvement may not correlate in the same individual. We identified a new splice site variant c.2803+5G>C (NM_004006) ClinVar VCV000803902, located in intron 22 of DMD in a Brazilian family that present a broad phenotypic and histological heterogeneity. One of the subjects had a typical Duchenne muscular dystrophy (DMD) phenotype, whereas the others had Becker muscular dystrophy (BMD). Cardiac involvement was remarkable in some of the BMD patients, but not in the DMD patient. Western blot analysis of skeletal muscle revealed much lower levels of calsequestrin in the most severely affected patient compared to his brother, whose phenotype is BMD, highlighting the potential role of proteins involved in skeletal muscle calcium homeostasis in differential degrees of dystrophinopathies.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2021 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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