A5010906930- Genomics and Rare Diseases
- Genomic variations and chromosomal abnormalities
- Sexual Differentiation and Disorders
- Esophageal and GI Pathology
- Urological Disorders and Treatments
- Connective tissue disorders research
- Tracheal and airway disorders
- Genetics and Neurodevelopmental Disorders
- Neurofibromatosis and Schwannoma Cases
- Intestinal Malrotation and Obstruction Disorders
- Congenital gastrointestinal and neural anomalies
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Prenatal Screening and Diagnostics
- Bone health and treatments
- Congenital Ear and Nasal Anomalies
- Congenital heart defects research
- Congenital Diaphragmatic Hernia Studies
- Hedgehog Signaling Pathway Studies
- Neurogenetic and Muscular Disorders Research
- RNA modifications and cancer
- Ocular Disorders and Treatments
- Soft tissue tumor case studies
- Renal and related cancers
- Chromosomal and Genetic Variations
- Cardiomyopathy and Myosin Studies
Erasmus University Rotterdam
2010-2025
Erasmus MC
2015-2025
Erasmus MC - Sophia Children’s Hospital
2008-2024
Cornell University
2021
Weill Cornell Medicine
2021
Universidade Estadual de Campinas (UNICAMP)
2012
Hendrix Genetics (Netherlands)
2010
Ghent University Hospital
2010
Antwerp University Hospital
2007-2010
University of Antwerp
2003-2005
Abstract Objective 17β-Hydroxysteroid dehydrogenase 3 deficiency (17β-HSDD) and 5α-reductase type 2 (5α-RD) are rare 46,XY differences of sex development (DSD). This study aims to enlarge the limited knowledge on long-term gonadal function pathology in these conditions. Design Retrospective multicentre cohort study. Methods Data phenotype, laboratory results, hormone treatment were collected from patients aged ≥16 years at time data collection with genetically confirmed 17β-HSDD 5α-RD 10...
NF1 mutations are the underlying cause of neurofibromatosis type 1 (NF1), a neuro-cardio-facio-cutaneous syndrome (NCFC). Because clinical overlap between NCFCs, genetic analysis is necessary to confirm diagnosis NF1. This report describes and findings 18 years molecular diagnostics in Netherlands. A pathogenic mutation was found 59.3% (1178/1985) index patients, mostly de novo (73.8%). The majority patients (64.3%) fulfilled National Institute Health criteria, 80.9% these patients....
Subtelomeric rearrangements are responsible for 5% to 10% of cases unexplained mental retardation. Despite their clinical relevance, methods screen these cytogenetically invisible abnormalities on a routine base scarce. We screened patients with idiopathic retardation subtelomeric aberrations using multiplex ligation-dependent probe amplification (MLPA). This recently developed technique is based PCR ligated probes hybridized chromosome ends. Currently, 41 telomeres can be in just two...
Megacystis Microcolon Intestinal Hypoperistalsis Syndrome (MMIHS) is a rare congenital disorder, in which heterozygous missense variants the Enteric Smooth Muscle actin γ-2 (ACTG2) gene have been recently identified. To investigate mechanism by ACTG2 lead to MMIHS, we screened cohort of eleven MMIHS patients, eight sporadic and three familial cases, performed immunohistochemistry, molecular modeling dynamics (MD) simulations, vitro assays. In all variant was expression detected intestinal...
Abstract Meier–Gorlin syndrome (MGS) is a rare autosomal recessive disorder characterized by primordial dwarfism, microtia, and patellar aplasia/hypoplasia. Recently, mutations in the ORC1 , ORC4 ORC6 CDT1 CDC6 genes, encoding components of pre‐replication complex, have been identified. This complex essential for DNA replication therefore are expected to impair cell proliferation consequently could globally reduce growth. However, detailed growth characteristics MGS patients not reported, so...
The lymphedema-lymphangiectasia-intellectual disability (Hennekam) syndrome (HS) is characterised by a widespread congenital lymph vessel dysplasia manifesting as lymphedema of the limbs and intestinal lymphangiectasia, accompanied unusual facial morphology, variable intellectual disabilities infrequently malformations. heterogeneous mutations in gene CCBE1 have been found responsible for only subset patients. We investigated whether it would be possible to predict presence mutation based on...
Biallelic damaging variants in ALPK3, encoding alpha-protein kinase 3, cause pediatric-onset cardiomyopathy with manifestations that are incompletely defined.We analyzed clinical of biallelic ALPK3 19 pediatric patients, including nine previously published cases. Among these, 11 loss-of-function (LoF) variants, seven compound LoF and deleterious missense one homozygous variant were identified. 18 live-born 8 exhibited neonatal dilated (44.4%; 95% CI: 21.5%-69.2%) subsequently transitioned...
PurposePathogenic variants in SETD1B have been associated with a syndromic neurodevelopmental disorder including intellectual disability, language delay, and seizures. To date, clinical features described for 11 patients (likely) pathogenic sequence variants. This study aims to further delineate the spectrum of SETD1B-related syndrome based on characterizing an expanded patient cohort.MethodsWe perform in-depth characterization cohort 36 unpublished individuals variants, describing their...
Multiple developmental and congenital disorders due to genetic variants or environmental exposures are associated with unique genome-wide alterations in DNA methylation (DNAm). Consequently, these patterns referred as DNAm signatures, can be leveraged for diagnostic purposes by developing artificial intelligence (AI) models that enable molecular subclassification of individuals. Notably, signature application has been particularly successful diagnosing individuals affected anomalies,...
Legius syndrome presents as an autosomal dominant condition characterized by café-au-lait macules with or without freckling and sometimes a Noonan-like appearance and/or learning difficulties. It is caused germline loss-of-function SPRED1 mutations member of the RAS-MAPK pathway syndromes. Most result in truncated protein only few inactivating missense have been reported. Since limited number patients has reported up until now, full clinical mutational spectrum still unknown. We report...
Thoracic aortic aneurysm and dissection (TAAD) are associated with connective tissue disorders like Marfan syndrome Loeys-Dietz syndrome, caused by mutations in the fibrillin-1, TGFβ-receptor 1- -2 genes, SMAD3 TGFβ2 but have also been ascribed to ACTA2 gene adults, spread throughout gene. We report on a novel de novo c.535C>T exon 6 leading p.R179C aminoacid substitution toddler girl primary pulmonary hypertension, persistent ductus arteriosus, extensive cerebral white matter lesions, fixed...
Abstract Congenital diaphragmatic hernia (CDH) is a common life-threatening birth defect. Recessive mutations in the FRAS1-related extracellular matrix 1 (FREM1) gene have been shown to cause bifid nose with or without anorectal and renal anomalies (BNAR) syndrome Manitoba oculotrichoanal (MOTA) syndrome, but not previously implicated development of CDH. We identified female child an isolated left-sided posterolateral CDH covered by membranous sac who had no features suggestive BNAR MOTA...
Objectives To compare the prenatal frame of reference omphalocele (ie, survival fetuses) with that after birth liveborn neonates), and to assess physical growth neurodevelopment in children minor or giant up 2 years age. Design We included fetuses neonates diagnosed 2000–2012. Physical (SD scores, SDS) mental motor development at 12 24 months were analysed using general linear models, outcomes compared norms. Giant was defined as defect ≥5 cm, liver protruding. Results 145 neonates. Of 126...
Abstract Introduction The aim of this retrospective cohort study was to determine the potential diagnostic yield prenatal whole exome sequencing in fetuses with structural anomalies on expert ultrasound scans and normal chromosomal microarray results. Material methods In period 2013‐2016, 391 pregnant women fetal who received results, were referred for additional genetic counseling opted molecular testing pre‐ and/or postnatally. Most couples only a targeted test 159 cases (40.7%) (broad...
Here we present the results of a study performed on 59 patients affected by Waardenburg syndrome (WS), 30 with I variant, 21 having type II, and 8 them being isolated cases without telecanthus. These belong to 37 families; main contributions conclusions are based detailed 25 these families, examined using standard procedures. All were as presence eight cardinal signs important for diagnosis condition; from each patient, many his/her normal relatives, control sample 300 individuals stratified...