Suzanne E. de Bruijn
A5004308908- Retinal Development and Disorders
- Hearing, Cochlea, Tinnitus, Genetics
- RNA regulation and disease
- CRISPR and Genetic Engineering
- Ocular Disorders and Treatments
- Advanced biosensing and bioanalysis techniques
- RNA and protein synthesis mechanisms
- interferon and immune responses
- Genomics and Phylogenetic Studies
- Vestibular and auditory disorders
- RNA Research and Splicing
- Genomics and Rare Diseases
- Cancer-related molecular mechanisms research
- Genomic variations and chromosomal abnormalities
- Retinal Diseases and Treatments
- Molecular Biology Techniques and Applications
- Genetic and Kidney Cyst Diseases
- Ear Surgery and Otitis Media
- Cytomegalovirus and herpesvirus research
- RNA modifications and cancer
- Genetics, Aging, and Longevity in Model Organisms
- Genetics and Neurodevelopmental Disorders
- Corneal Surgery and Treatments
- Connexins and lens biology
- Receptor Mechanisms and Signaling
Radboud University Nijmegen
2018-2025
Radboud University Medical Center
2018-2025
University Medical Center
2021-2025
Maastricht University
2024-2025
Radboud Institute for Molecular Life Sciences
2021
The cause of autosomal-dominant retinitis pigmentosa (adRP), which leads to loss vision and blindness, was investigated in families lacking a molecular diagnosis. A refined locus for adRP on Chr17q22 (RP17) delineated through genotyping genome sequencing, leading the identification structural variants (SVs) that segregate with disease. Eight different complex SVs were characterized 22 adRP-affected >300 affected individuals. All RP17 had breakpoints within genomic region spanning YPEL2...
Sequencing technologies have long limited the comprehensive investigation of large transcripts associated with inherited retinal diseases (IRDs) like Usher syndrome, which involves 11 genes up to 19.6 kb. To address this, we used PacBio long-read mRNA isoform sequencing (Iso-Seq) following standard library preparation and an optimized workflow enrich for in human neural retina. While our achieved 15 kb, this was insufficient syndrome-associated USH2A ADGRV1, 18.9 kb respectively. overcome...
Structural variants (SVs) play an important role in inherited retinal diseases (IRD). Although the identification of SVs significantly improved upon availability genome sequencing, it is expected that involvement IRDs higher than anticipated. We revisited short-read sequencing data to enhance gene-disruptive SVs.Optical mapping was performed improve SV detection sequencing-negative cases. In addition, reanalysis interpretation and re-establish prioritization criteria.In a monoallelic USH2A...
A significant number of individuals with a rare disorder such as Usher syndrome (USH) and (non-)syndromic autosomal recessive retinitis pigmentosa (arRP) remain genetically unexplained. Therefore, we assessed subjects suspected
Introduction: Retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA) are two groups of inherited retinal diseases (IRDs) where the rod photoreceptors degenerate followed by cone retina. A genetic diagnosis for IRDs is challenging since >280 genes associated with these conditions. While whole exome sequencing (WES) commonly used diagnostic facilities, costs required infrastructure prevent its global applicability. Previous studies have shown cost-effectiveness sequence analysis using...
The U4 small nuclear RNA (snRNA) forms a duplex with the U6 snRNA and, together U5 and ∼30 proteins, is part of U4/U6.U5 tri-snRNP complex, located at core major spliceosome. Recently, recurrent de novo variants in RNA, transcribed from RNU4-2 gene, least two other RNU genes were discovered to cause neurodevelopmental disorder. We detected inherited heterozygous (n.18_19insA n.56T>C) four out five RNU6 paralogues (n.55_56insG n.56_57insG) 135 individuals 62 families non-syndromic retinitis...
Abstract Splice prediction tools can be used to identify splice-altering variants in patients with inherited diseases. Since splicing is tissue-specific, a predicted splice defect may vary depending on the tissue of interest. Current often neglect junctions from human neural retina, which lead misinterpretation benign and pathogenic retinal diseases (IRDs). To address this issue, we developed retina-specific tool based model architecture SpliceAI. In addition retraining existing using...
Background Hearing loss is one of the most prevalent disabilities worldwide, and has a significant impact on quality life. The adult-onset type condition highly heritable but genetic causes are largely unknown, which in contrast to childhood-onset hearing loss. Methods Family cohort studies included exome sequencing characterisation phenotype. Ex vivo protein expression addressed functional effect DNA variant. Results An in-frame deletion 12 nucleotides RIPOR2 was identified as penetrant...
CRISPR-Cas9-based genome-editing is a highly efficient and cost-effective method to generate zebrafish loss-of-function alleles. However, introducing patient-specific variants into the genome with CRISPR-Cas9 remains challenging. Targeting options can be limited by predetermined genetic context, efficiency of homology-directed DNA repair pathway relatively low. Here, we illustrate our approach develop knock-in models using two previously associated hereditary sensory deficits. We employ...
Background Retinitis pigmentosa (RP) shows substantial genetic heterogeneity. It has been estimated that in approximately 60%–80% of RP cases, the diagnosis can be found using whole exome sequencing (WES). In this study, purpose was to identify causative variants individuals with genetically unexplained retinal disease, which included one consanguineous family two affected siblings and case RP. Methods To defect, WES performed both probands, clinical analysis performed. obtain insight into...
The human neural retina is a complex tissue with abundant alternative splicing and more than 10% of genetic variants linked to inherited retinal diseases (IRDs) alter splicing. Traditional short-read RNA-sequencing methods have been used for understanding retina-specific but limitations in detailing transcript isoforms. To address this, we generated proteogenomic atlas that combines PacBio long-read data mass spectrometry whole genome sequencing three healthy samples. We identified nearly...
Inherited retinal dystrophies (IRDs) are characterized by photoreceptor dysfunction or degeneration. Clinical and phenotypic overlap between IRDs makes the genetic diagnosis very challenging comprehensive genomic approaches for accurate frequently required. While there previous studies on in Pakistan, causative genes variants still unknown a significant portion of patients. Therefore, is need to expand knowledge spectrum Pakistan. Here, we recruited 52 affected 53 normal individuals from 15...
Introduction Autosomal dominant retinitis pigmentosa type 17 (adRP, RP17) is caused by complex structural variants (SVs) affecting a locus on chromosome (chr17q22). The SVs disrupt the 3D regulatory landscape altering topologically associating domain (TAD) structure of locus, creating novel TAD structures (neo-TADs) and ectopic enhancer-gene contacts. Currently, screening for RP17-associated not included in routine diagnostics given complexity lack cost-effective detection methods. aim this...
Pathogenic variants in SLC26A4 have been associated with autosomal recessive hearing loss (arHL) and a unilateral or bilateral enlarged vestibular aqueduct (EVA). is the second most frequently mutated gene arHL. Despite strong genotype-phenotype correlation, significant part of cases remains genetically unresolved. In this study, we investigated cohort 28 Dutch index diagnosed HL combination an EVA but without (M0) single (M1) pathogenic variant SLC26A4. To explore missing heritability,...
Anophthalmia and microphthalmia (A/M) are among the most severe congenital developmental eye disorders. Despite advancements in genome screening technologies, more than half of A/M patients do not receive a molecular diagnosis. We included seven consanguineous families affected with from Pakistani cohort an unknown basis. Single gene testing FOXE3 was performed, followed by sequencing for unsolved probands order to establish genetic diagnosis these families. All were provided The identified...
Introduction: Inherited retinal dystrophies (IRDs) can be caused by variants in more than 280 genes. The ATP-binding cassette transporter type A4 (ABCA4) gene is one of these genes and has been linked to Stargardt disease 1 (STGD1), fundus flavimaculatus, cone-rod dystrophy (CRD), pan-retinal CRD. Approximately 25% the reported ABCA4 affect RNA splicing. In most cases, it necessary perform a functional assay determine effect variants. Methods: Whole genome sequencing (WGS) was performed...
The human neural retina is a complex tissue with abundant alternative splicing and more than 10% of genetic variants linked to inherited retinal diseases (IRDs) alter splicing. Traditional short-read RNA-sequencing methods have been used for understanding retina-specific but limitations in detailing transcript isoforms. To address this, we generated proteogenomic atlas that combines PacBio long-read data mass spectrometry whole genome sequencing three healthy samples. We identified nearly...
ABSTRACT Sequencing technologies have long limited the comprehensive investigation of large transcripts associated with inherited retinal diseases (IRDs) like Usher syndrome, which involves 11 genes up to 19.6 kb. To address this, we used PacBio long-read mRNA isoform sequencing (Iso-Seq) following standard library preparation and an optimized workflow enrich for in human neural retina. While our achieved 15 kb, this was insufficient syndrome-associated USH2A ADGRV1 , 18.9 kb respectively....
Abstract Pathogenic variants in SLC26A4 have been associated with autosomal recessive hearing loss (arHL) and a unilateral or bilateral enlarged vestibular aqueduct (EVA). is the second most frequently mutated gene arHL. Despite strong genotype-phenotype correlation, significant part of cases remains genetically unresolved. In this study, we investigated cohort 28 Dutch index diagnosed HL combination an EVA but without (M0) single (M1) pathogenic variant . To explore missing heritability,...