Floor A.M. Duijkers
A5040740602- Genetic factors in colorectal cancer
- Neuroblastoma Research and Treatments
- Colorectal Cancer Screening and Detection
- Cancer Genomics and Diagnostics
- Cancer, Hypoxia, and Metabolism
- Mitochondrial Function and Pathology
- Nuclear Structure and Function
- Genetic Neurodegenerative Diseases
- Cardiomyopathy and Myosin Studies
- Soft tissue tumor case studies
- Epigenetics and DNA Methylation
- Genetics and Neurodevelopmental Disorders
- Hedgehog Signaling Pathway Studies
- Neurofibromatosis and Schwannoma Cases
- BRCA gene mutations in cancer
- Cancer Diagnosis and Treatment
- Congenital Diaphragmatic Hernia Studies
- Neurological diseases and metabolism
- RNA Research and Splicing
- PI3K/AKT/mTOR signaling in cancer
- Renal and related cancers
- Cancer therapeutics and mechanisms
- Sarcoma Diagnosis and Treatment
- Phagocytosis and Immune Regulation
- Cancer-related gene regulation
University of Amsterdam
2016-2024
Amsterdam University Medical Centers
2019-2024
Amsterdam UMC Location Vrije Universiteit Amsterdam
2018-2020
University Medical Center
2018-2020
University Hospital and Clinics
2018-2020
Amsterdam UMC Location University of Amsterdam
2018
Erasmus MC - Sophia Children’s Hospital
2011-2014
Boston Children's Hospital
2010-2013
Variants in the KIF1A gene can cause autosomal recessive spastic paraplegia 30, hereditary sensory neuropathy, or (de novo) dominant mental retardation type 9. More recently, variants have also been described a few cases with paraplegia. Here, we describe 20 24 patients from clinical exome sequencing cohort of 347 individuals mostly 'pure' In these patients, was slowly progressive and pure, but highly variable disease onset (0-57 years). Segregation analyses showed de novo occurrence seven...
Rubinstein-Taybi syndrome (RTS) is an archetypical genetic that characterised by intellectual disability, well-defined facial features, distal limb anomalies and atypical growth, among numerous other signs symptoms. It caused variants in either of two genes ( CREBBP , EP300 ) which encode for the proteins CBP p300, both have a function transcription regulation histone acetylation. As group international experts national support groups dedicated to syndrome, we realised marked heterogeneity...
To compare colorectal cancer (CRC) incidences in carriers of pathogenic variants the MMR genes PLSD and IMRC cohorts, which only former included mandatory colonoscopy surveillance for all participants.
Variants in CLCN4, which encodes the chloride/hydrogen ion exchanger CIC-4 prominently expressed brain, were recently described to cause X-linked intellectual disability and epilepsy. We present detailed phenotypic information on 52 individuals from 16 families with CLCN4-related disorder: 5 affected females 2 males a de novo variant CLCN4 (6 previously unreported) 27 males, 3 15 asymptomatic female carriers 9 inherited variants (4 unreported). Intellectual ranged borderline profound....
Abstract Context Pituitary stalk interruption syndrome (PSIS) consists of a small/absent anterior pituitary lobe, an interrupted/absent stalk, and ectopic posterior lobe. Mendelian forms PSIS are detected infrequently (<5%), polygenic etiology has been suggested. GLI2 variants have reported at relatively high frequency in PSIS. Objective To provide further evidence for non-Mendelian, Methods Exome sequencing (trio approach) 20 patients with isolated In addition to searching...
Abstract Abnormal gut motility is a feature of several mitochondrial encephalomyopathies, and mutations in genes such as TYMP POLG, have been linked to these rare diseases. The human genome encodes three DNA ligases, which only one, ligase III (LIG3), has splice variant crucial for health. We investigated the effect reduced LIG3 activity resulting dysfunction seven patients from independent families, who showed common occurrence dysmotility neurological manifestations reminiscent...
PTEN Hamartoma Tumor Syndrome (PHTS) is a rare syndrome with broad phenotypic spectrum, including increased risks of breast (BC, 67%-78% at age 60 years), endometrial (EC, 19%-28%), and thyroid cancer (TC, 6%-38%). Current are likely overestimated due to ascertainment bias. We aimed provide more accurate personalized risks.This was European, adult PHTS cohort study data from medical files, registries, and/or questionnaires. Cancer hazard ratios were assessed Kaplan-Meier Cox regression...
Abstract Chung-Jansen syndrome is a neurodevelopmental disorder characterized by intellectual disability, behavioral problems, obesity and dysmorphic features. It caused pathogenic variants in the PHIP gene that encodes for Pleckstrin homology domain-interacting protein, which part of an epigenetic modifier protein complex. Therefore, we hypothesized haploinsufficiency may impact genome-wide DNA methylation (DNAm). We assessed DNAm profiles affected individuals with likely Infinium...
Introduction Lynch syndrome (LS) is a hereditary cancer caused by (likely) pathogenic variants (LP/P) in DNA mismatch repair genes, including MSH6. It associated with elevated lifetime risks for colorectal (CRC), endometrial (EC), and other malignancies. However, specific to MSH6-associated LS, particularly non-colorectal cancers, remain poorly defined. This study aims provide refined risk estimates individuals MSH6 LP/P. Methods We conducted retrospective cohort of 360 families 1117 known...
Hotspot mutations in the promoter of telomerase reverse transcriptase ( TERT ) gene have been recently reported human cancers and proposed as a novel mechanism activation. To explore tumors originating from adrenal gland extra-adrenal paraganglia, set 253 (38 adrenocortical carcinomas (ACCs), 127 pheochromocytomas (PCCs), 18 paragangliomas (ea PGLs), 37 head neck PGLs (HN 33 peripheral neuroblastic tumors) was selected along with 16 neuroblastoma (NBL) two ACC cell lines to assess by Sanger...
Diagnosis of Lynch syndrome (LS) caused by a pathogenic germline MSH6 variant may be complicated discordant immunohistochemistry (IHC) and/or microsatellite stable (MSS) phenotype. This study aimed to identify the various causes phenotypes colorectal cancer (CRC) and endometrial (EC) in MSH6-associated LS. Data were collected from Dutch family clinics. Carriers (likely) diagnosed with CRC or EC categorized based on an instability (MSI)/IHC test outcome that might fail result diagnosis LS...
In pediatric neuroblastoma (NBL), high anaplastic lymphoma kinase (ALK) levels appear to be correlated with an unfavorable prognosis, regardless of ALK mutation status. This suggests a therapeutic role for inhibitors in NBL patients. We examined the correlation between ALK, phosphorylated (pALK) and downstream signaling proteins response inhibition large panel both mutated wild type (WT) cell lines. measured protein by western blot inhibitor sensitivity (TAE684) viability assays 19 lines...
Biallelic MSH3 germline variants are a rare cause of adenomatous polyposis as yet reported in two small families only. We describe the phenotype third family, largest thus far, with related to compound heterozygous pathogenic variants. The index patient was 55-years old male diagnosed rectal cancer and (cumulatively 52 polyps), family history colorectal unknown cause. Next-generation sequencing copy number variation analysis panel genes associated revealed gene. Nine out 11 siblings were...
Pathogenic PTEN germline variants cause Hamartoma Tumor Syndrome (PHTS), a rare disease with variable genotype and phenotype. Knowledge about these spectra genotype-phenotype associations could help diagnostics potentially lead to personalized care. Therefore, we assessed the PHTS phenotype spectrum in large cohort study.Information was collected of 510 index patients pathogenic or likely (LP/P) (n = 467) uncertain significance. Genotype-phenotype were using logistic regression analyses...
Renal cell carcinoma (RCC) is the most common kidney tumor in adults. RCC rare children, although its incidence increases second decade of life. medullary (RMC) a and often aggressive subtype characterized by complete loss SMARCB1/INI1, predominantly diagnosed patients with sickle disease or -trait. Here, we describe pediatric young adult patient clinicopathological characteristics similar to RMC but without hemoglobinopathies. These tumors are currently classified as “RCC unclassified...
Introduction Pigmentary mosaicism (PM) manifests by pigmentation anomalies along Blaschko’s lines and represents a clue toward the molecular diagnosis of syndromic intellectual disability (ID). Together with new insights on role for lysosomal signalling in embryonic stem cell differentiation, mutations X-linked transcription factor 3 ( TFE3 ) have recently been reported five patients. Functional analysis suggested these to result ectopic nuclear gain functions. Materials methods Subsequent...
Neurofibromatosis type 1 (NF1) is caused by loss-of-function variants in the NF1 gene. Approximately 10% of these affect RNA splicing and are either missed conventional DNA diagnostics or misinterpreted silico predictions. Therefore, a targeted RNAseq-based approach was designed to detect pathogenic associated variants. For this method extracted from lymphocytes, followed RNAseq. Next, an in-house developed tool (QURNAs) used calculate enrichment score (ERS) for each event. This thoroughly...