Daan M. Panneman
A5054646611- Retinal Development and Disorders
- Mitochondrial Function and Pathology
- Advanced biosensing and bioanalysis techniques
- Retinal Diseases and Treatments
- Genetics and Neurodevelopmental Disorders
- Metabolism and Genetic Disorders
- Ocular Disorders and Treatments
- Genetics, Aging, and Longevity in Model Organisms
- Endoplasmic Reticulum Stress and Disease
- CRISPR and Genetic Engineering
- RNA regulation and disease
- ATP Synthase and ATPases Research
- Pancreatic function and diabetes
- Retinoids in leukemia and cellular processes
- Circadian rhythm and melatonin
- Genomics and Rare Diseases
- Dermatological and Skeletal Disorders
- Lysosomal Storage Disorders Research
- Hedgehog Signaling Pathway Studies
- Genomic variations and chromosomal abnormalities
- Ocular Diseases and Behçet’s Syndrome
- Biosensors and Analytical Detection
- Cellular transport and secretion
- Adipose Tissue and Metabolism
- Genetic and Kidney Cyst Diseases
Radboud University Medical Center
2017-2025
Radboud University Nijmegen
2017-2025
University Medical Center
2023-2024
Radboud Institute for Molecular Life Sciences
2019-2023
University of Amsterdam
2020-2022
Amsterdam University Medical Centers
2020-2022
Amalia Kinderziekenhuis
2020-2021
Mayo Clinic
2020
WinnMed
2020
Epilepsy, intellectual and cortical sensory deficits, psychiatric manifestations are the most frequent of mitochondrial diseases. How dysfunction affects neural structure function remains elusive, mostly because a lack proper in vitro neuronal model systems with dysfunction. Leveraging induced pluripotent stem cell technology, we differentiated excitatory neurons (iNeurons) normal (low heteroplasmy) impaired (high on an isogenic nuclear DNA background from patients common pathogenic m.3243A...
Gitelman syndrome is the most frequent hereditary salt-losing tubulopathy characterized by hypokalemic alkalosis and hypomagnesemia. caused biallelic pathogenic variants in SLC12A3, encoding Na+-Cl- cotransporter (NCC) expressed distal convoluted tubule. Pathogenic of CLCNKB, HNF1B, FXYD2, or KCNJ10 may result same renal phenotype syndrome, as they can lead to reduced NCC activity. For approximately 10 percent patients with a phenotype, genotype unknown.We identified mitochondrial DNA...
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...
Purpose: To determine the profile of inflammation-related proteins and complement system factors in plasma CRB1-associated inherited retinal dystrophies (CRB1-IRDs). Methods: We used Olink Explore 384 Inflammation II panel for targeted proteomics 30 cases 29 controls (cohort I) to identify immune pathways involved CRB1-IRDs. Genotyping was performed cohort I a second 123 patients from 14 countries 1292 II). Results: A significant shift cascade observed proteomes CRB1-IRD (enrichment cascade,...
Inherited macular dystrophies (iMDs) are a group of genetic disorders, which affect the central region retina. To investigate basis iMDs, we used single-molecule Molecular Inversion Probes to sequence 105 maculopathy-associated genes in 1352 patients diagnosed with iMDs. Within this cohort, 39.8% were considered genetically explained by 460 different variants 49 distinct 73 novel variants, some affecting splicing. The top five most frequent causative ABCA4 (37.2%), PRPH2 (6.7%), CDHR1...
NGLY1 encodes the enzyme N-glycanase that is involved in degradation of glycoproteins as part endoplasmatic reticulum-associated pathway. Variants this gene have been described to cause a multisystem disease characterized by neuromotor impairment, neuropathy, intellectual disability, and dysmorphic features. Here, we describe four patients with pathogenic variants NGLY1. As clinical features laboratory results suggested mitochondrial disease, muscle biopsy had performed. Biochemical analysis...
Macular degenerations (MDs) are a subgroup of retinal disorders characterized by central vision loss. Knowledge is still lacking on the extent genetic and nongenetic factors influencing inherited MD (iMD) age-related (AMD) expression. Single molecule Molecular Inversion Probes (smMIPs) have proven effective in sequencing ABCA4 gene patients with Stargardt disease to identify associated coding noncoding variation, however many remain genetically unexplained. We hypothesized that missing...
The evolutionarily conserved soluble adenylyl cyclase (sAC, ADCY10) mediates cAMP signaling exclusively in intracellular compartments. Because sAC activity is sensitive to local concentrations of ATP, bicarbonate, and free Ca2+, potentially an important metabolic sensor. Nonetheless, little known about how regulates energy metabolism intact cells. In this study, we demonstrated that both pharmacological genetic suppression resulted increased lactate secretion decreased pyruvate multiple cell...
Phosphoglucomutase 1 (PGM1) is a key enzyme for the regulation of energy metabolism from glycogen and glycolysis, as it catalyzes interconversion glucose 1-phosphate 6-phosphate. PGM1 deficiency an autosomal recessive disorder characterized by highly heterogenous clinical spectrum, including hypoglycemia, cleft palate, liver dysfunction, growth delay, exercise intolerance, dilated cardiomyopathy. Abnormal protein glycosylation has been observed in this disease. Oral supplementation with...
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...
Deregulated energy homeostasis represents a hallmark of aging and results from complex gene-by-environment interactions. Here, we discovered that reducing the expression gene ech-6 encoding enoyl-CoA hydratase remitted fat diet-induced deleterious effects on lifespan in Caenorhabditis elegans, while basal was important for survival under normal dietary conditions. Lipidomics revealed supplementation ech-6-silenced worms had marginal lipid profiles, suggesting an alternative utilization...
Summary Epilepsy, intellectual and cortical sensory deficits psychiatric manifestations are among the most frequent of mitochondrial diseases. Yet, how dysfunction affects neural structure function remains largely elusive. This is mostly due to lack a proper in vitro translational neuronal model system(s) with impaired energy metabolism. Leveraging induced pluripotent stem cell technology, from cohort patients common pathogenic m.3243A>G variant encephalomyopathy, lactic acidosis...
Obtaining a genetic diagnosis for IRDs is challenging as more than 280 genes are associated with these conditions. Next‐generation sequencing approaches such whole exome and genome often used but their costs required infrastructure still prohibit global applicability. Previous studies have shown the cost‐effectiveness of sequence analysis using single molecule Molecular Inversion Probes (smMIPs) in cohort patients diagnosed Stargardt disease other maculopathies. Recently, we developed two...
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...
Inherited retinal diseases (IRDs) are clinically complex and genetically heterogeneous visual impairment disorders with varying penetrance severity. Disease-causing variants in at least 289 nuclear mitochondrial genes have been implicated their pathogenesis.
Inherited retinal diseases (IRDs) are clinically complex and genetically heterogeneous visual impairment disorders with varying penetrance severity. Disease-causing variants in at least 289 nuclear mitochondrial genes have been implicated their pathogenesis. In the current study, we performed exome sequencing on a 51 years-old Ashkenazi Jewish patient non-syndromic retinitis pigmentosa (RP) identified compound heterozygous CLRN1 gene: known pathogenic missense [p.(N48K)] novel deep intronic...
Macular dystrophies are a group of individually rare but collectively common inherited retinal characterised by central vision loss and visual acuity. Single molecule Molecular Inversion Probes (smMIPs) have proved effective in identifying genetic variants causing macular dystrophy. Here, previously established smMIPs panel tailored for genes associated with diseases has been used to examine 57 UK dystrophy cases, achieving high solve rate 63.2% (36/57). Among 27 bi-allelic STGD1 only three...
Abstract Background Macular diseases (MDs) are a subgroup of retinal disorders characterized by central vision loss that represent major cause impairment. Despite the identification numerous genes associated with inherited MD (iMD) and risk factors age-related (AMD), extent genetic non-genetic influence expression is still not fully explained. Single molecule Molecular Inversion Probes (smMIPs) have proven effective in sequencing ABCA4 gene patients Stargardt disease cost-effective manner to...
Abstract 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...
Abstract Objective To determine the profile of inflammation-related proteins and complement system factors in serum CRB1 -associated inherited retinal dystrophies ( -IRDs). Design A case-control study. Subjects, Participants, and/or Controls cohort 30 Dutch -IRD patients 29 healthy controls (HC) (Cohort I), a second 123 from 14 countries 1292 II) were used this Methods Quantitative 370-plex targeted proteomics blood plasma genotyping single nucleotide variant (SNV) rs7535263 CFH gene. Main...