A5064626101- Connective tissue disorders research
- Aortic Disease and Treatment Approaches
- Genomic variations and chromosomal abnormalities
- Aortic aneurysm repair treatments
- Cardiac Valve Diseases and Treatments
- Genetics and Neurodevelopmental Disorders
- Metabolism and Genetic Disorders
- Congenital heart defects research
- Protease and Inhibitor Mechanisms
- Chromosomal and Genetic Variations
- Cardiovascular Health and Disease Prevention
- Cardiovascular Issues in Pregnancy
- Genomics and Rare Diseases
- Cardiovascular Function and Risk Factors
- Genetic factors in colorectal cancer
- TGF-β signaling in diseases
- Cellular transport and secretion
- RNA modifications and cancer
- RNA regulation and disease
- Congenital Anomalies and Fetal Surgery
- Neurogenetic and Muscular Disorders Research
- Autism Spectrum Disorder Research
- Ubiquitin and proteasome pathways
- Prenatal Screening and Diagnostics
- Gastrointestinal disorders and treatments
Leiden University Medical Center
2016-2025
Leiden University
2000-2020
The diagnosis of Marfan syndrome (MFS) relies on defined clinical criteria (Ghent nosology), outlined by international expert opinion to facilitate accurate recognition this genetic aneurysm and improve patient management counselling. These Ghent criteria, comprising a set major minor manifestations in different body systems, have proven work well since with improving molecular techniques, confirmation the is possible over 95% patients. However, concerns current nosology are that some...
Aneurysms-osteoarthritis syndrome (AOS) is a new autosomal dominant syndromic form of thoracic aortic aneurysms and dissections characterised by the presence arterial tortuosity, mild craniofacial, skeletal cutaneous anomalies, early-onset osteoarthritis. AOS caused mutations in SMAD3 gene.A cohort 393 patients with without mutation FBN1, TGFBR1 TGFBR2 was screened for SMAD3. The originated from Netherlands, Belgium, Switzerland USA. clinical phenotype total 45 eight different families...
IGF-I is a key factor in intrauterine development and postnatal growth metabolism. The secretion of utero not dependent on GH, whereas childhood adult life, seems to be mainly controlled by as revealed from studies patients with GHRH receptor GH mutations. In 55-yr-old male, the first child consanguineous parents, presenting severe retardation, microcephaly, sensorineural deafness, we found homozygous G A nucleotide substitution gene changing valine 44 into methione. inactivating nature...
The Loeys–Dietz syndrome (LDS) is a connective tissue disorder affecting the cardiovascular, skeletal, and ocular system. Most typically, LDS patients present with aortic aneurysms arterial tortuosity, hypertelorism, bifid/broad uvula or cleft palate. Initially, mutations in transforming growth factor-β (TGF-β) receptors (TGFBR1 TGFBR2) were described to cause LDS, hereby leading impaired TGF-β signaling. More recently, ligands, TGFB2 TGFB3, as well intracellular downstream effectors of...
Mitochondrial disorders, characterized by clinical symptoms and/or OXPHOS deficiencies, are caused pathogenic variants in mitochondrial genes. However, some of these genes can lead to manifestations which overlap with other neuromuscular diseases, be non-mitochondrial as well. found the DNA (mtDNA) or any 1,500 nuclear a function. We have performed two-step next-generation sequencing approach cohort 117 patients, mostly children, whom disease-cause could likely possibly explain phenotype. A...
BACKGROUND: Vascular Ehlers-Danlos syndrome (vEDS) is a rare connective tissue disorder with high risk for arterial, bowel, and uterine rupture, caused by heterozygous pathogenic variants in COL3A1 . The aim of this cohort study to provide further insights into the natural history vEDS describe genotype-phenotype correlations Dutch multicenter optimize patient care increase awareness disease. METHODS: Individuals throughout Netherlands were included. phenotype was charted retrospective...
ABSTRACT Objective We aim to increase knowledge on pregnancy and delivery risks in vascular Ehlers–Danlos Syndrome (vEDS). Our outcomes can contribute establishing future guidelines for management women with vEDS. Design Retrospective multicentre cohort study. Setting Women vEDS due pathogenic/likely pathogenic (P/LP) COL3A1 variants are at increased risk arterial dissection pregnancy‐related complications during delivery. Population a P/LP variant were included from 2019 until 2021. Methods...
We report three families with arterial aneurysms and dissections in which variants predicted to be pathogenic were identified SMAD2. Moreover, one variant occurred de novo a proband unaffected parents. SMAD2 is strong candidate gene for given its role the TGF-β signaling pathway. Furthermore, although SMAD3 probably have functionally distinct roles cell signaling, they are structurally very similar. Our findings indicate that mutations associated accordance observation patients genes...
SMC1A encodes one of the proteins cohesin complex. variants are known to cause a phenotype resembling Cornelia de Lange syndrome (CdLS). Exome sequencing has allowed recognizing in individuals with encephalopathy epilepsy who do not resemble CdLS. We performed an international, interdisciplinary study on 51 for physical and behavioral characteristics, compare results those 67 NIPBL variants. For Netherlands all were studied, both without CdLS phenotype. Individuals can CdLS, but...
Background Marfan syndrome (MFS) is a pleiotropic genetic disorder with major features in cardiovascular, ocular and skeletal systems, associated large clinical variability. Numerous studies reveal an involvement of TGF-β signaling. However, the contribution tissue inflammation not addressed so far. Methodology/Principal Findings Here we showed that both are up-regulated patients MFS. We analyzed transcriptome-wide gene expression 55 MFS using Affymetrix Human Exon 1.0 ST Array levels...
Simultaneous analysis of multiple genes using next-generation sequencing (NGS) technology has become widely available. Copy-number variations (CNVs) in disease-associated have emerged as a cause for several hereditary disorders. CNVs are, however, not routinely detected NGS analysis. The aim this study was to assess the diagnostic yield and prevalence our panel Hereditary Thoracic Aortic Disease (H-TAD)-associated genes. Eight hundred ten patients suspected H-TAD were analyzed by targeted 21...
Abstract CHD8 has been reported as an autism susceptibility/intellectual disability gene but emerging evidence suggests that it additionally causes overgrowth phenotype. This study reports 27 unrelated patients with pathogenic or likely variants (25 null variants, two missense variants) and a male:female ratio of 21:6 (3.5:1, p < .01). All presented intellectual disability, 85% in the mild moderate range, had height and/or head circumference ≥2 standard deviations above mean, meeting our...
Abstract We describe 19 unrelated individuals with submicroscopic deletions involving 10p15.3 characterized by chromosomal microarray (CMA). Interestingly, to our knowledge, only two isolated, deletion have been reported date; however, limited clinical information is available for these probands and the deleted region has not molecularly mapped. Comprehensive history was obtained 12 of described in this study. Common features among include: cognitive/behavioral/developmental differences...
Abstract Purpose: To study age‐related change in aortic stiffness patients with Marfan syndrome (MFS) versus healthy volunteers using velocity‐encoded (VE) MRI. Materials and Methods: Twenty‐five MFS (age range, 18–63 years; mean age 36 ± 14 years, 13 men) 25 age‐/gender‐matched were examined VE‐MRI. Aortic was expressed by pulse wave velocity (PWV), assessed the proximal distal part of aorta total aorta. PWV compared between age‐relation determined linear regression. Results: significantly...
Background Musculocontractural Ehlers−Danlos syndrome is caused by biallelic loss-of-function variants in CHST14 (mcEDS- ) or DSE ). Although 48 patients 33 families with mcEDS- have been reported, the spectrum of pathogenic variants, accurate prevalence various manifestations and detailed natural history not systematically investigated. Methods We collected comprehensive clinical molecular information regarding previously reported newly identified through international collaborations....
Infantile juvenile polyposis is a rare disease with severe gastrointestinal symptoms and grave clinical course. Recently, 10q23 microdeletions involving the PTEN BMPR1A genes were found in four patients infantile polyposis. It was hypothesized that combined synergistic effect of deletion both would explain condition. Subsequently, however, patient larger including same but mild phenotype identified. Here, we present additional genes. The sizes deletions analyzed using single nucleotide...