Imperial College London
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ProfessorSanjayPrasad

Faculty of Medicine, National Heart & Lung Institute

Professor of Cardiomyopathy
 
 
 
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Contact

 

+44 (0)20 7352 8121s.prasad

 
 
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Location

 

CMR UnitRoyal BromptonRoyal Brompton Campus

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Summary

 

Publications

Citation

BibTex format

@article{Mazzarotto:2021:10.1038/s41436-020-01049-x,
author = {Mazzarotto, F and Hawley, MH and Beltrami, M and Beekman, L and De, Marvao A and McGurk, K and Statton, B and Boschi, B and Girolami, F and Roberts, AM and Lodder, EM and Allouba, M and Romeih, S and Aguib, Y and Baksi, J and Pantazis, A and Prasad, SK and Cerbai, E and Yacoub, M and O'Regan, D and Cook, S and Ware, J and Funke, B and Olivotto, I and Bezzina, C and Barton, P and Walsh, R},
doi = {10.1038/s41436-020-01049-x},
journal = {Genetics in Medicine},
pages = {856--864},
title = {Systematic large-scale assessment of the genetic architecture of left ventricular non-compaction reveals diverse aetiologies},
url = {http://dx.doi.org/10.1038/s41436-020-01049-x},
volume = {23},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Purpose: To characterise the genetic architecture of left ventricular non-compaction (LVNC) and investigate the extent to which it may represent a distinct pathology or a secondary phenotype associated with other cardiac diseases.Methods: We performed rare variant association analysis with 840 LVNC cases and 125,748 gnomAD population controls, and compared results to similar analyses on dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM). Results: We observed substantial genetic overlap indicating that LVNC often represents a phenotypic variation of DCM or HCM. In contrast, truncating variants (TV) in MYH7, ACTN2 and PRDM16 were uniquely associated with LVNC and may reflect a distinct LVNC aetiology. In particular, MYH7 TV, generally considered non-pathogenic for cardiomyopathies, were 20-fold enriched in LVNC cases over controls. MYH7 TV heterozygotes identified in the UK Biobank and healthy volunteer cohorts also displayed significantly greater non-compaction compared to matched controls. RYR2 exon deletions and HCN4 transmembrane variants were also enriched in LVNC, supporting prior reports of association with arrhythmogenic LVNC phenotypes.Conclusions: LVNC is characterised by substantial genetic overlap with DCM/HCM but is also associated with distinct non-compaction and arrhythmia aetiologies. These results will enable enhanced application of LVNC genetic testing and help to distinguish pathological from physiological non-compaction.
AU  - Mazzarotto,F
AU  - Hawley,MH
AU  - Beltrami,M
AU  - Beekman,L
AU  - De,Marvao A
AU  - McGurk,K
AU  - Statton,B
AU  - Boschi,B
AU  - Girolami,F
AU  - Roberts,AM
AU  - Lodder,EM
AU  - Allouba,M
AU  - Romeih,S
AU  - Aguib,Y
AU  - Baksi,J
AU  - Pantazis,A
AU  - Prasad,SK
AU  - Cerbai,E
AU  - Yacoub,M
AU  - O'Regan,D
AU  - Cook,S
AU  - Ware,J
AU  - Funke,B
AU  - Olivotto,I
AU  - Bezzina,C
AU  - Barton,P
AU  - Walsh,R
DO  - 10.1038/s41436-020-01049-x
EP  - 864
PY  - 2021///
SN  - 1098-3600
SP  - 856
TI  - Systematic large-scale assessment of the genetic architecture of left ventricular non-compaction reveals diverse aetiologies
T2  - Genetics in Medicine
UR  - http://dx.doi.org/10.1038/s41436-020-01049-x
UR  - https://www.nature.com/articles/s41436-020-01049-x
UR  - http://hdl.handle.net/10044/1/85034
VL  - 23
ER  -
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