Imperial College London
Alternate

ProfessorThomasBrand

Faculty of Medicine, National Heart & Lung Institute

Chair in Developmental Dynamics
 
 
 
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Contact

 

+44 (0)20 7594 8744t.brand Website CV

 
 
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Assistant

 

Miss Cheryl Costello +44 (0)20 7594 3001

 
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Location

 

433ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{De:2019:10.1212/nxg.0000000000000321,
author = {De, Ridder W and Nelson, I and Asselbergh, B and De, Paepe B and Beuvin, M and Ben, Yaou R and Masson, C and Boland, A and Deleuze, J-F and Maisonobe, T and Eymard, B and Symoens, S and Schindler, R and Brand, T and Johnson, K and Töpf, A and Straub, V and De, Jonghe P and De, Bleecker JL and Bonne, G and Baets, J},
doi = {10.1212/nxg.0000000000000321},
journal = {Neurology Genetics},
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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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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.
AU  - De,Ridder W
AU  - Nelson,I
AU  - Asselbergh,B
AU  - De,Paepe B
AU  - Beuvin,M
AU  - Ben,Yaou R
AU  - Masson,C
AU  - Boland,A
AU  - Deleuze,J-F
AU  - Maisonobe,T
AU  - Eymard,B
AU  - Symoens,S
AU  - Schindler,R
AU  - Brand,T
AU  - Johnson,K
AU  - Töpf,A
AU  - Straub,V
AU  - De,Jonghe P
AU  - De,Bleecker JL
AU  - Bonne,G
AU  - Baets,J
DO  - 10.1212/nxg.0000000000000321
PY  - 2019///
SN  - 2376-7839
TI  - Muscular dystrophy with arrhythmia caused by loss-of-function mutations in BVES
T2  - Neurology Genetics
UR  - http://dx.doi.org/10.1212/nxg.0000000000000321
UR  - http://hdl.handle.net/10044/1/69086
VL  - 5
ER  -
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