A5020654126- Retinal Development and Disorders
- CRISPR and Genetic Engineering
- Genomics and Phylogenetic Studies
- Genetic and Kidney Cyst Diseases
- RNA regulation and disease
- Genomics and Rare Diseases
- Genetic Syndromes and Imprinting
- interferon and immune responses
- Advanced biosensing and bioanalysis techniques
- Genetics and Neurodevelopmental Disorders
- Retinal Diseases and Treatments
- Integrated Circuits and Semiconductor Failure Analysis
- Hedgehog Signaling Pathway Studies
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Cellular transport and secretion
- Renal Transplantation Outcomes and Treatments
- RNA Research and Splicing
- RNA and protein synthesis mechanisms
Radboud University Nijmegen
2018-2022
Radboud University Medical Center
2018-2022
University Medical Center
2022
Inherited retinal diseases (IRDs) are a major cause of visual impairment. These clinically heterogeneous disorders caused by pathogenic variants in more than 270 genes. As 30-40% cases remain genetically unexplained following conventional genetic testing, we aimed to obtain diagnosis an IRD cohort which the was not found using whole-exome sequencing or targeted capture sequencing. We performed whole-genome (WGS) identify causative 100 unresolved cases. After initial prioritization, in-depth...
Pathogenic variants in the ATP-binding cassette transporter A4 (ABCA4) gene cause a continuum of retinal disease phenotypes, including Stargardt disease. Noncanonical splice site (NCSS) and deep-intronic constitute large fraction disease-causing alleles, defining functional consequences which remains challenge. We aimed to determine effect on splicing nine previously reported or unpublished NCSS variants, one near exon variant ABCA4, using vitro assays human embryonic kidney 293T cells....
Purpose: Inherited retinal diseases are a group of clinically and genetically heterogeneous disorders with approximately 270 genes involved. IMPG2 is associated adult-onset vitelliform macular dystrophy. Here, we investigated two unrelated patients dystrophy to identify the underlying genetic cause. Methods: Whole-exome sequencing identified putative causal complex allele consisting c.3023-15T>A c.3023G>A (p.(Gly1008Asp)) in both individuals. To assess its effect, vitro splice assays HEK293T...
Background Inherited retinal diseases (IRDs) can be caused by variants in >270 genes. The Bardet-Biedl syndrome 1 ( BBS1 ) gene is one of these genes and may associated with syndromic non-syndromic autosomal recessive retinitis pigmentosa (RP). Here, we identified a branchpoint variant assessed its pathogenicity vitro functional analysis. Methods Whole genome sequencing was performed for three unrelated monoallelic cases RP. A fourth case received MGCM 105 panel Functional analysis using...
The lack of molecular diagnoses in rare genetic diseases can be explained by limitations current standard genomic technologies. Upcoming long-read techniques have complementary strengths to overcome these limitations, with a particular strength identifying structural variants. By using optical genome mapping and sequencing, we aimed identify the pathogenic variant large family X-linked choroideremia. In this family, aberrant splicing exon 12 choroideremia gene CHM was detected 2003, but...
Pathogenic variants in RPE65 lead to retinal diseases, causing a vision impairment. In this work, we investigated the pathomechanism behind frequent variant, c.11+5G>A. Previous silico predictions classified change as splice variant. Our prediction using novel software’s suggested 124-nt exon elongation containing premature stop codon. This was validated midigenes-based approaches. Similar results were observed patient-derived induced pluripotent stem cells (iPSC) and photoreceptor...
Human Leukocyte Antigen (HLA) has an important role in presenting self and non-self-antigens to T-cell receptors on T lymphocytes. For tissue transplantation the possibility of graft rejection, these HLA antigens surface donor recipient's cells should be checked.In this study, a novel technique was used for typing by cloning sequencing. The most polymorphic exons HLA-A, HLA-B, HLA-DRB1 five unrelated persons were cloned into T-vector. Afterward, sequencing data analyzed using new computer...