Suzanne de Bruijn

TABLE OF CONTENTS Chapter 1 Introduction 11 Chapter 1.1 General introduction 11 Chapter 1.2 The impact of modern technologies on molecular diagnostic success rates, with a focus on inherited retinal dystrophy and hearing loss 35 Chapter 2 Homozygous variants in KIAA1549 , encoding a ciliary protein, are associated with autosomal recessive retinitis pigmentosa 77 Chapter 3 DFNA21 99 Chapter 3.1 A RIPOR2 in-frame deletion is a frequent and highly penetrant cause of adult-onset hearing loss 99 Chapter 3.2 The development of a genetic therapy for DFNA21 using allele-specific antisense oligonucleotides 147 Chapter 4 Structural variants create new topological associated domains and ectopic retinal enhancer-gene contact in dominant retinitis pigmentosa 167 Chapter 5 Exploring the missing heritability in subjects with hearing loss, enlarged vestibular aqueducts, and a single or no pathogenic SLC26A4 variant 231 Chapter 6 General discussion and perspectives 281 Chapter 7 Summary 319 Chapter 7.1 Summary 319 Chapter 7.2 Samenvatting 323 Chapter 8 Appendix Data management plan 331 List of publications 333 PhD portfolio 335 About the author 337 Acknowledgements 339 Abbreviations 347