Imperial College London
Alternate

DrDeborahMorris-Rosendahl

Faculty of Medicine, National Heart & Lung Institute

Honorary Senior Research Fellow
 
 
 
//

Contact

 

+44 (0)20 7351 8412d.morris-rosendahl

 
 
//

Location

 

2091Royal BromptonRoyal Brompton Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Guimier:2021:10.1038/s41436-021-01296-6,
author = {Guimier, A and Achleitner, MT and de, Bellaing AM and Edwards, M and de, Pontual L and Mittal, K and Dunn, KE and Grove, ME and Tysoe, CJ and Dimartino, C and Cameron, J and Kanthi, A and Shukla, A and van, den Broek F and Chatterjee, D and Alston, CL and Knowles, CV and Brett, L and Till, JA and Homfray, T and French, P and Spentzou, G and Elserafy, NA and Lichkus, KS and Sankaran, BP and Kennedy, HL and George, PM and Kidd, A and Wortmann, SB and Fisk, DG and Koopmann, TT and Rafiq, MA and Merker, JD and Parikh, S and Ahimaz, P and Weintraub, RG and Ma, AS and Turner, C and Ellaway, CJ and Phillips, LK and Thorburn, DR and Chung, WK and Kana, SL and Faye-Petersen, OM and Thompson, ML and Janin, A and McLeod, K and McGowan, R and McFarland, R and Girisha, KM and Morris-Rosendahl, DJ and Hurst, ACE and Turner, CLS and Hamilton, RM and Taylor, RW and Bajolle, F and Gordon, CT and Amiel, J and Mayr, JA and Doudney, K},
doi = {10.1038/s41436-021-01296-6},
journal = {Genetics in Medicine},
pages = {2415--2425},
title = {PPA2-associated sudden cardiac death: extending the clinical and allelic spectrum in 20 new families},
url = {http://dx.doi.org/10.1038/s41436-021-01296-6},
volume = {23},
year = {2021}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - PurposeBiallelic hypomorphic variants in PPA2, encoding the mitochondrial inorganic pyrophosphatase 2 protein, have been recently identified in individuals presenting with sudden cardiac death, occasionally triggered by alcohol intake or a viral infection. Here we report 20 new families harboring PPA2 variants.MethodsSynthesis of clinical and molecular data concerning 34 individuals harboring five previously reported PPA2 variants and 12 novel variants, 11 of which were functionally characterized.ResultsAmong the 34 individuals, only 6 remain alive. Twenty-three died before the age of 2 years while five died between 14 and 16 years. Within these 28 cases, 15 died of sudden cardiac arrest and 13 of acute heart failure. One case was diagnosed prenatally with cardiomyopathy. Four teenagers drank alcohol before sudden cardiac arrest. Progressive neurological signs were observed in 2/6 surviving individuals. For 11 variants, recombinant PPA2 enzyme activities were significantly decreased and sensitive to temperature, compared to wild-type PPA2 enzyme activity.ConclusionWe expand the clinical and mutational spectrum associated with PPA2 dysfunction. Heart failure and sudden cardiac arrest occur at various ages with inter- and intrafamilial phenotypic variability, and presentation can include progressive neurological disease. Alcohol intake can trigger cardiac arrest and should be strictly avoided.
AU  - Guimier,A
AU  - Achleitner,MT
AU  - de,Bellaing AM
AU  - Edwards,M
AU  - de,Pontual L
AU  - Mittal,K
AU  - Dunn,KE
AU  - Grove,ME
AU  - Tysoe,CJ
AU  - Dimartino,C
AU  - Cameron,J
AU  - Kanthi,A
AU  - Shukla,A
AU  - van,den Broek F
AU  - Chatterjee,D
AU  - Alston,CL
AU  - Knowles,CV
AU  - Brett,L
AU  - Till,JA
AU  - Homfray,T
AU  - French,P
AU  - Spentzou,G
AU  - Elserafy,NA
AU  - Lichkus,KS
AU  - Sankaran,BP
AU  - Kennedy,HL
AU  - George,PM
AU  - Kidd,A
AU  - Wortmann,SB
AU  - Fisk,DG
AU  - Koopmann,TT
AU  - Rafiq,MA
AU  - Merker,JD
AU  - Parikh,S
AU  - Ahimaz,P
AU  - Weintraub,RG
AU  - Ma,AS
AU  - Turner,C
AU  - Ellaway,CJ
AU  - Phillips,LK
AU  - Thorburn,DR
AU  - Chung,WK
AU  - Kana,SL
AU  - Faye-Petersen,OM
AU  - Thompson,ML
AU  - Janin,A
AU  - McLeod,K
AU  - McGowan,R
AU  - McFarland,R
AU  - Girisha,KM
AU  - Morris-Rosendahl,DJ
AU  - Hurst,ACE
AU  - Turner,CLS
AU  - Hamilton,RM
AU  - Taylor,RW
AU  - Bajolle,F
AU  - Gordon,CT
AU  - Amiel,J
AU  - Mayr,JA
AU  - Doudney,K
DO  - 10.1038/s41436-021-01296-6
EP  - 2425
PY  - 2021///
SN  - 1098-3600
SP  - 2415
TI  - PPA2-associated sudden cardiac death: extending the clinical and allelic spectrum in 20 new families
T2  - Genetics in Medicine
UR  - http://dx.doi.org/10.1038/s41436-021-01296-6
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000685392000001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://www.nature.com/articles/s41436-021-01296-6
UR  - http://hdl.handle.net/10044/1/91531
VL  - 23
ER  -
Download