Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/139675
Citations | ||
Scopus | Web of Science® | Altmetric |
---|---|---|
?
|
?
|
Type: | Journal article |
Title: | PPA2-associated sudden cardiac death: extending the clinical and allelic spectrum in 20 new families |
Author: | Guimier, A. Achleitner, M.T. Moreau de Bellaing, A. Edwards, M. de Pontual, L. Mittal, K. Dunn, K.E. Grove, M.E. Tysoe, C.J. Dimartino, C. Cameron, J. Kanthi, A. Shukla, A. van den Broek, F. Chatterjee, D. Alston, C.L. Knowles, C.V. Brett, L. Till, J.A. Homfray, T. et al. |
Citation: | Genetics in Medicine, 2021; 23(12):2415-2425 |
Publisher: | SPRINGERNATURE |
Issue Date: | 2021 |
ISSN: | 1098-3600 1530-0366 |
Statement of Responsibility: | Anne Guimier ... Liza K. Phillips ... et al. |
Abstract: | Purpose: Biallelic 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. Methods: Synthesis of clinical and molecular data concerning 34 individuals harboring five previously reported PPA2 variants and 12 novel variants, 11 of which were functionally characterized. Results: Among 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. Conclusion: We 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. |
Keywords: | Cardiomyopathies Death, Sudden, Cardiac Inorganic Pyrophosphatase Mitochondrial Proteins Mutation Alleles Adolescent Child, Preschool |
Rights: | © The Author(s) 2021. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons. org/licenses/by/4.0/. |
DOI: | 10.1038/s41436-021-01296-6 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/GNT1113531 |
Published version: | http://dx.doi.org/10.1038/s41436-021-01296-6 |
Appears in Collections: | Medicine publications |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
hdl_139675.pdf | Published version | 1.14 MB | Adobe PDF | View/Open |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.