Imperial College London
Alternate

DrPiersDaubeney

Faculty of Medicine, National Heart & Lung Institute

Professor of Practice (Paediatric Cardiology)
 
 
 
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Contact

 

+44 (0)20 7351 8430p.daubeney

 
 
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Location

 

Royal BromptonRoyal Brompton Campus

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Summary

 

Publications

Citation

BibTex format

@article{Sifrim:2016:10.1038/ng.3627,
author = {Sifrim, A and Hitz, M-P and Wilsdon, A and Breckpot, J and Al, Turki SH and Thienpont, B and McRae, J and Fitzgerald, TW and Singh, T and Swaminathan, GJ and Prigmore, E and Rajan, D and Abdul-Khaliq, H and Banka, S and Bauer, UMM and Bentham, J and Berger, F and Bhattacharya, S and Bu'Lock, F and Canham, N and Colgiu, I-G and Cosgrove, C and Cox, H and Daehnert, I and Daly, A and Danesh, J and Fryer, A and Gewillig, M and Hobson, E and Hoff, K and Homfray, T and Kahlert, A-K and Ketley, A and Kramer, H-H and Lachlan, K and Lampe, AK and Louw, JJ and Manickara, AK and Manase, D and McCarthy, KP and Metcalfe, K and Moore, C and Newbury-Ecob, R and Omer, SO and Ouwehand, WH and Park, S-M and Parker, MJ and Pickardt, T and Pollard, MO and Robert, L and Roberts, DJ and Sambrook, J and Setchfield, K and Stiller, B and Thornborough, C and Toka, O and Watkins, H and Williams, D and Wright, M and Mital, S and Daubeney, PEF and Keavney, B and Goodship, J and Abu-Sulaiman, RM and Klaassen, S and},
doi = {10.1038/ng.3627},
journal = {Nature Genetics},
pages = {1060--1065},
title = {Distinct genetic architectures for syndromic and nonsyndromic congenital heart defects identified by exome sequencing},
url = {http://dx.doi.org/10.1038/ng.3627},
volume = {48},
year = {2016}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Congenital heart defects (CHDs) have a neonatal incidence of 0.8–1% (refs. 1,2). Despite abundant examples of monogenic CHD in humans and mice, CHD has a low absolute sibling recurrence risk (~2.7%)3, suggesting a considerable role for de novo mutations (DNMs) and/or incomplete penetrance4, 5. De novo protein-truncating variants (PTVs) have been shown to be enriched among the 10% of 'syndromic' patients with extra-cardiac manifestations6, 7. We exome sequenced 1,891 probands, including both syndromic CHD (S-CHD, n = 610) and nonsyndromic CHD (NS-CHD, n = 1,281). In S-CHD, we confirmed a significant enrichment of de novo PTVs but not inherited PTVs in known CHD-associated genes, consistent with recent findings8. Conversely, in NS-CHD we observed significant enrichment of PTVs inherited from unaffected parents in CHD-associated genes. We identified three genome-wide significant S-CHD disorders caused by DNMs in CHD4, CDK13 and PRKD1. Our study finds evidence for distinct genetic architectures underlying the low sibling recurrence risk in S-CHD and NS-CHD.
AU  - Sifrim,A
AU  - Hitz,M-P
AU  - Wilsdon,A
AU  - Breckpot,J
AU  - Al,Turki SH
AU  - Thienpont,B
AU  - McRae,J
AU  - Fitzgerald,TW
AU  - Singh,T
AU  - Swaminathan,GJ
AU  - Prigmore,E
AU  - Rajan,D
AU  - Abdul-Khaliq,H
AU  - Banka,S
AU  - Bauer,UMM
AU  - Bentham,J
AU  - Berger,F
AU  - Bhattacharya,S
AU  - Bu'Lock,F
AU  - Canham,N
AU  - Colgiu,I-G
AU  - Cosgrove,C
AU  - Cox,H
AU  - Daehnert,I
AU  - Daly,A
AU  - Danesh,J
AU  - Fryer,A
AU  - Gewillig,M
AU  - Hobson,E
AU  - Hoff,K
AU  - Homfray,T
AU  - Kahlert,A-K
AU  - Ketley,A
AU  - Kramer,H-H
AU  - Lachlan,K
AU  - Lampe,AK
AU  - Louw,JJ
AU  - Manickara,AK
AU  - Manase,D
AU  - McCarthy,KP
AU  - Metcalfe,K
AU  - Moore,C
AU  - Newbury-Ecob,R
AU  - Omer,SO
AU  - Ouwehand,WH
AU  - Park,S-M
AU  - Parker,MJ
AU  - Pickardt,T
AU  - Pollard,MO
AU  - Robert,L
AU  - Roberts,DJ
AU  - Sambrook,J
AU  - Setchfield,K
AU  - Stiller,B
AU  - Thornborough,C
AU  - Toka,O
AU  - Watkins,H
AU  - Williams,D
AU  - Wright,M
AU  - Mital,S
AU  - Daubeney,PEF
AU  - Keavney,B
AU  - Goodship,J
AU  - Abu-Sulaiman,RM
AU  - Klaassen,S
AU  - Wright,CF
AU  - Firth,HV
AU  - Barrett,JC
AU  - Devriendt,K
AU  - FitzPatrick,DR
AU  - Brook,JD
AU  - Hurles,ME
DO  - 10.1038/ng.3627
EP  - 1065
PY  - 2016///
SN  - 1061-4036
SP  - 1060
TI  - Distinct genetic architectures for syndromic and nonsyndromic congenital heart defects identified by exome sequencing
T2  - Nature Genetics
UR  - http://dx.doi.org/10.1038/ng.3627
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000382398800018&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/42666
VL  - 48
ER  -
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