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Muscular dystrophy with arrhythmia caused by loss-of-function mutations in BVES

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Organization
Abstract
Objective: To study the genetic and phenotypic spectrum of patients harboring recessive mutations in BVES. Methods: We performed whole-exome sequencing in a multicenter cohort of 1929 patients with a suspected hereditary myopathy, showing unexplained limb-girdle muscular weakness and/or elevated creatine kinase levels. Immunohistochemistry and mRNA experiments on patients' skeletal muscle tissue were performed to study the pathogenicity of identified loss-of-function (LOF) variants in BVES. Results: We identified 4 individuals from 3 families harboring homozygous LOF variants in BVES, the gene that encodes for Popeye domain containing protein 1 (POPDC1). Patients showed skeletal muscle involvement and cardiac conduction abnormalities of varying nature and severity, but all exhibited at least subclinical signs of both skeletal muscle and cardiac disease. All identified mutations lead to a partial or complete loss of function of BVES through nonsense-mediated decay or through functional changes to the POPDC1 protein. Conclusions: We report the identification of homozygous LOF mutations in BVES, causal in a young adult-onset myopathy with concomitant cardiac conduction disorders in the absence of structural heart disease. These findings underline the role of POPDC1, and by extension, other members of this protein family, in striated muscle physiology and disease. This disorder appears to have a low prevalence, although it is probably underdiagnosed because of its striking phenotypic variability and often subtle yet clinically relevant manifestations, particularly concerning the cardiac conduction abnormalities.
Keywords
LIMB-GIRDLE, PROTEINS

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MLA
De Ridder, Willem et al. “Muscular Dystrophy with Arrhythmia Caused by Loss-of-function Mutations in BVES.” NEUROLOGY-GENETICS 5.2 (2019): n. pag. Print.
APA
De Ridder, Willem, Nelson, I., Asselbergh, B., De Paepe, B., Beuvin, M., Ben Yaou, R., Masson, C., et al. (2019). Muscular dystrophy with arrhythmia caused by loss-of-function mutations in BVES. NEUROLOGY-GENETICS, 5(2).
Chicago author-date
De Ridder, Willem, Isabelle Nelson, Bob Asselbergh, Boel De Paepe, Maud Beuvin, Rabah Ben Yaou, Cécile Masson, et al. 2019. “Muscular Dystrophy with Arrhythmia Caused by Loss-of-function Mutations in BVES.” Neurology-genetics 5 (2).
Chicago author-date (all authors)
De Ridder, Willem, Isabelle Nelson, Bob Asselbergh, Boel De Paepe, Maud Beuvin, Rabah Ben Yaou, Cécile Masson, Anne Boland, Jean-François Deleuze, Thierry Maisonobe, Bruno Eymard, Sofie Symoens, Roland Schindler, Thomas Brand, Katherine Johnson, Ana Töpf, Volker Straub, Peter De Jonghe, Jan De Bleecker, Gisèle Bonne, and Jonathan Baets. 2019. “Muscular Dystrophy with Arrhythmia Caused by Loss-of-function Mutations in BVES.” Neurology-genetics 5 (2).
Vancouver
1.
De Ridder W, Nelson I, Asselbergh B, De Paepe B, Beuvin M, Ben Yaou R, et al. Muscular dystrophy with arrhythmia caused by loss-of-function mutations in BVES. NEUROLOGY-GENETICS. 2019;5(2).
IEEE
[1]
W. De Ridder et al., “Muscular dystrophy with arrhythmia caused by loss-of-function mutations in BVES,” NEUROLOGY-GENETICS, vol. 5, no. 2, 2019.
@article{8617142,
  abstract     = {Objective: To study the genetic and phenotypic spectrum of patients harboring recessive mutations in BVES.
Methods: We performed whole-exome sequencing in a multicenter cohort of 1929 patients with a suspected hereditary myopathy, showing unexplained limb-girdle muscular weakness and/or elevated creatine kinase levels. Immunohistochemistry and mRNA experiments on patients' skeletal muscle tissue were performed to study the pathogenicity of identified loss-of-function (LOF) variants in BVES.
Results: We identified 4 individuals from 3 families harboring homozygous LOF variants in BVES, the gene that encodes for Popeye domain containing protein 1 (POPDC1). Patients showed skeletal muscle involvement and cardiac conduction abnormalities of varying nature and severity, but all exhibited at least subclinical signs of both skeletal muscle and cardiac disease. All identified mutations lead to a partial or complete loss of function of BVES through nonsense-mediated decay or through functional changes to the POPDC1 protein.
Conclusions: We report the identification of homozygous LOF mutations in BVES, causal in a young adult-onset myopathy with concomitant cardiac conduction disorders in the absence of structural heart disease. These findings underline the role of POPDC1, and by extension, other members of this protein family, in striated muscle physiology and disease. This disorder appears to have a low prevalence, although it is probably underdiagnosed because of its striking phenotypic variability and often subtle yet clinically relevant manifestations, particularly concerning the cardiac conduction abnormalities.},
  articleno    = {e321},
  author       = {De Ridder, Willem and Nelson, Isabelle and Asselbergh, Bob and De Paepe, Boel and Beuvin, Maud and Ben Yaou, Rabah and Masson, Cécile and Boland, Anne and Deleuze, Jean-François and Maisonobe, Thierry and Eymard, Bruno and Symoens, Sofie and Schindler, Roland and Brand, Thomas and Johnson, Katherine and Töpf, Ana and Straub, Volker and De Jonghe, Peter and De Bleecker, Jan and Bonne, Gisèle and Baets, Jonathan},
  issn         = {2376-7839},
  journal      = {NEUROLOGY-GENETICS},
  keywords     = {LIMB-GIRDLE,PROTEINS},
  language     = {eng},
  number       = {2},
  pages        = {11},
  title        = {Muscular dystrophy with arrhythmia caused by loss-of-function mutations in BVES},
  url          = {http://dx.doi.org/10.1212/nxg.0000000000000321},
  volume       = {5},
  year         = {2019},
}

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