University of Groningen
Paediatric cardiomyopathies
Herkert, Johanna Cornelia
DOI:
10.33612/diss.97534698
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Publication date:
2019
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Citation for published version (APA):
Herkert, J. C. (2019). Paediatric cardiomyopathies: an evolving landscape of genetic aetiology and
diagnostic applications. Rijksuniversiteit Groningen. https://doi.org/10.33612/diss.97534698
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Paediatric cardiomyopathies
An evolving landscape of genetic aetiology
and diagnostic applications
ISBN (printed version): 978-94-034-1899-5 ISBN (electronic version): 978-94-034-1898-8 Cover design and layout: © evelienjagtman.com Printing: Ipskamp Printing, Enschede, the Netherlands
Printing of this thesis was financially supported by the Graduate School of Medical Sciences, University Medical Center Groningen, the Netherlands
© 2019, J.C. Herkert, the Netherlands
All rights reserved. No part of this thesis may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, without prior permission of the author or, when appropriate, of the publisher of the publications included in this thesis.
Paediatric cardiomyopathies
An evolving landscape of genetic aetiology and diagnostic applications
Proefschrift
ter verkrijging van de graad van doctor aan de Rijksuniversiteit Groningen
op gezag van de
rector magnificus prof. dr. C. Wijmenga en volgens besluit van het College voor Promoties.
De openbare verdediging zal plaatsvinden op woensdag 16 oktober 2019 om 11.00 uur
door
Johanna Cornelia Herkert
geboren op 27 februari 1981 te Epe
Promotores
Prof. dr. I.M. van Langen Prof. dr. M.P. van den Berg
Copromotor
Dr. J.D.H. Jongbloed
Beoordelingscommissie
Prof. dr. M.M.A.M. Mannens Prof. dr. N.A. Blom
Paranimfen
Mieke Kerstjens Cyrille Herkert
Voor Maria, Marije, Jeffrey, Engbert, Yoni, Antine, Rianne, Sharona, Sophie, Dylan, Jade, Asya, Mart, Lauri, Eslem, Naomi, Kick, Sander, Tiger, Hendrik, Jeroen, Michiel, Mart, Marlies, Felicia, Emam, Kaiden, Twan, Stef, Ilse, Jarno, Matthijs, Eva, Oemaima, Sylvia, Abdulsamet, Peter, Rick, Jefta, Mart, Jette, Koen, Monica, Meike, Noelle,
Contents
Part I Introduction
Chapter 1 General Introduction & Aims and outline of this thesis 11 Chapter 2 Clinical utility gene card for: dilated cardiomyopathy (CMD) 39 Chapter 3 Compound heterozygous or homozygous truncating MYBPC3
mutations cause lethal cardiomyopathy with features of noncompaction and septal defects
57
Part II Yield and strategies for genetic testing and data analysis
Chapter 4 Toward an effective exome-based genetic testing strategy in paediatric dilated cardiomyopathy
81 Chapter 5 Improving the diagnostic yield of exome-sequencing by predicting
gene-phenotype associations using large-scale gene expression analysis
147
Part III Rare and novel genes
Chapter 6 Novel SPEG mutations in congenital myopathies: genotype-phenotype correlations
185 Chapter 7 Biallelic truncating mutations in ALPK3 cause severe paediatric
cardiomyopathy
201 Chapter 8 Expanding the clinical and genetic spectrum of ALPK3 variants:
phenotypes identified in paediatric cardiomyopathy patients and adults with heterozygous variants
229
Chapter 9 Homozygous damaging SOD2 variant causes lethal neonatal dilated cardiomyopathy
287
Part IV Summary and general discussion
Chapter 10 Summary 319
Chapter 11 Discussion and future perspectives 327
Appendix
Nederlandse samenvatting List of abbreviations
List of authors and affiliations Curriculum vitae List of publications Dankwoord 347 255 361 373 377 385
