Publications by authors named "Kerkhof J"

Background: Contacts between people and free-ranging animals have a potential to cause viral disease epidemics when novel viruses are exchanged. The Netherlands has approximately 18 native bat species, of which some generally use buildings for roosting, and has a dense human population. Frequent indirect and direct contacts between bats and humans could thus be expected, however, this has hardly been studied.

View Article and Find Full Text PDF

Over two decades ago, a primigravid female presented with concern for recurrence of an adverse phenotype affecting her three brothers. The three brothers presented with intellectual disability, developmental delay, behavior problems and dysmorphic features. The screening tools available at the time revealed an FGD1 variant present in all three brothers, their mother being a carrier, absent in their unaffected uncle, and absent in the proband herself.

View Article and Find Full Text PDF

Pathogenic heterozygous variants in CHD4 cause Sifrim-Hitz-Weiss syndrome, a neurodevelopmental disorder associated with brain anomalies, heart defects, macrocephaly, hypogonadism, and additional features with variable expressivity. Most individuals have non-recurrent missense variants, complicating variant interpretation. A few were reported with truncating variants, and their role in disease is unclear.

View Article and Find Full Text PDF

Neurodevelopmental disorders (NDD) comprise clinical conditions with high genetic heterogeneity and a notable enrichment of genes involved in regulating chromatin structure and function. The EHMT1/2 epigenetic complex plays a crucial role in repression of gene transcription in a highly tissue- and temporal-specific manner. Mutations resulting in heterozygous loss-of-function (LoF) of EHMT1 are implicated in Kleefstra syndrome 1 (KS1).

View Article and Find Full Text PDF

Purpose: is one of the most frequently mutated genes in intellectual disability cohorts. Thus, far few adult-aged patients with -related disorder have been described, which limits our understanding of the disease's natural history and our ability to counsel patients and their families.

Methods: Data on patients aged 18+ years with -related disorder were collected through an online questionnaire completed by clinicians and parents.

View Article and Find Full Text PDF

Background: This study aimed to evaluate patient satisfaction and usage patterns of bone conduction devices (BCDs) for hearing rehabilitation, focusing on both users and non-users. Specific objectives included assessing reasons for non-use, exploring patient perceptions of BCD efficacy, and examining complications associated with BCD implantation.

Methods: A monocentric investigation was conducted at the Department of Ear, Nose, and Throat Diseases, Head and Neck Surgery at General Hospital Sint-Jan, Bruges.

View Article and Find Full Text PDF

Rubinstein-Taybi syndrome (RSTS) is a rare autosomal dominant neurodevelopmental disorder linked to haploinsufficiency of CREBBP (RSTS1) and EP300 (RSTS2) genes. Characteristic features often include distinctive facial traits, broad thumbs and toes, short stature, and various degrees of intellectual disability. The clinical presentation of RSTS is notably variable, making it challenging to establish a clear genotype-phenotype correlation, except for specific variants which cause the allelic Menke-Hennekam syndrome.

View Article and Find Full Text PDF

Developmental Delay with Gastrointestinal, Cardiovascular, Genitourinary, and Skeletal Abnormalities syndrome (DEGCAGS, MIM #619488) is caused by biallelic, loss-of-function (LoF) ZNF699 variants, and is characterized by variable neurodevelopmental disability, discordant organ anomalies among full siblings and infant mortality. ZNF699 encodes a KRAB zinc finger protein of unknown function. We aimed to investigate the genotype-phenotype spectrum of DEGCAGS and the possibility of a diagnostic DNA methylation episignature, to facilitate the diagnosis of a highly variable condition lacking pathognomonic clinical findings.

View Article and Find Full Text PDF
Article Synopsis
  • ARID1A and ARID1B duplications are linked to Coffin-Siris syndrome, but ARID1B duplications have not been previously associated with a specific clinical phenotype until now.
  • A study analyzed 16 cases of ARID1A and 13 cases of ARID1B duplications, revealing that ARID1A duplications resulted in more severe symptoms, including intellectual disabilities and growth delays, while both groups displayed similar features.
  • The research identified unique DNA methylation patterns in ARID1A duplication patients, which differ from those with loss-of-function variants, suggesting the presence of a distinct clinical phenotype for both ARID1A and ARID1B duplications, indicating a new type of
View Article and Find Full Text PDF

Aquaculture is expected to play a vital role in solving the challenge of sustainably providing the growing world population with healthy and nutritious food. Pathogen outbreaks are a major risk for the sector, so early detection and a timely response are crucial. This can be enabled by monitoring the pathogen levels in aquaculture facilities.

View Article and Find Full Text PDF

We report a 40-year-old African American female with a novel variant in exon 8 of DNA methyltransferase 3 alpha (DNMT3A), (NM_022552.4: c.905G>C, p.

View Article and Find Full Text PDF
Article Synopsis
  • Sequence-based genetic testing finds causative variants in about 50% of cases of developmental and epileptic encephalopathies (DEEs), but DNA methylation changes in these cases have not been thoroughly explored.
  • This study analyzed genome-wide DNA methylation in blood samples from 582 individuals with unresolved DEEs, identifying rare methylation patterns and potential genetic causes in 12 of these cases.
  • The research highlights the effectiveness of DNA methylation analysis in diagnosing DEEs, showing a 2% diagnostic yield, and provides insights into the CHD2 gene's pathophysiology using advanced sequencing methods.
View Article and Find Full Text PDF

Purpose: Valproic acid or valproate is an effective antiepileptic drug; however, embryonic exposure to valproate can result in a teratogenic disorder referred to as fetal valproate syndrome (OMIM #609442). Currently there are no diagnostic biomarkers for the condition. This study aims to define an episignature biomarker for teratogenic antenatal exposure to valproate.

View Article and Find Full Text PDF

The term "recurrent constellations of embryonic malformations" (RCEM) is used to describe a number of multiple malformation associations that affect three or more body structures. The causes of these disorders are currently unknown, and no diagnostic marker has been identified. Consequently, providing a definitive diagnosis in suspected individuals is challenging.

View Article and Find Full Text PDF

Context: Hyperinsulinemic hypoglycemia (HI) can be the presenting feature of Kabuki syndrome (KS), which is caused by loss-of-function variants in KMT2D or KDM6A. As these genes play a critical role in maintaining methylation status in chromatin, individuals with pathogenic variants have a disease-specific epigenomic profile -an episignature.

Objective: We evaluated the pathogenicity of three novel partial KDM6A duplications identified in three individuals presenting with neonatal-onset HI without typical features of KS at the time of genetic testing.

View Article and Find Full Text PDF
Article Synopsis
  • - The AUTS2 gene family includes AUTS2 and FBRSL1, both of which may play roles in neurogenesis and transcription regulation, but FBRSL1's exact function remains unclear despite its relatedness to AUTS2.
  • - A patient with a de novo truncating variant in FBRSL1 exhibited clinical symptoms linked to this genetic alteration, prompting research into how additional genetic factors, including duplications from both parents, might modulate the phenotype.
  • - In-depth analysis combining protein structure predictions and genomic data suggests FBRSL1 could influence neurodevelopment and potentially be involved in distinct clinical syndromes, emphasizing the importance of genetic and epigenetic interactions in understanding these conditions.
View Article and Find Full Text PDF
Article Synopsis
  • * This study shows that specific non-truncating mutations in ARID1B disrupt protein structure, causing harmful aggregation in cells, while still maintaining protein levels.
  • * Findings support the idea that these non-truncating variants could cause disease, encouraging a reevaluation of previously ambiguous variants and enhancing genetic diagnosis for Coffin-Siris syndrome.
View Article and Find Full Text PDF

The shift to a genotype-first approach in genetic diagnostics has revolutionized our understanding of neurodevelopmental disorders, expanding both their molecular and phenotypic spectra. Kleefstra syndrome (KLEFS1) is caused by EHMT1 haploinsufficiency and exhibits broad clinical manifestations. EHMT1 encodes euchromatic histone methyltransferase-1-a pivotal component of the epigenetic machinery.

View Article and Find Full Text PDF

Blepharophimosis with intellectual disability (BIS) is a recently recognized disorder distinct from Nicolaides-Baraister syndrome that presents with distinct facial features of blepharophimosis, developmental delay, and intellectual disability. BIS is caused by pathogenic variants in SMARCA2, that encodes the catalytic subunit of the superfamily II helicase group of the BRG1 and BRM-associated factors (BAF) forming the BAF complex, a chromatin remodeling complex involved in transcriptional regulation. Individuals bearing variants within the bipartite nuclear localization (BNL) signal domain of ADNP present with the neurodevelopmental disorder known as Helsmoortel-Van Der Aa Syndrome (HVDAS).

View Article and Find Full Text PDF
Article Synopsis
  • * A study identified 25 individuals with new variations in the MSL2 gene, who exhibited NDD symptoms such as developmental delays, coordination problems, and autism spectrum disorder, along with other health concerns.
  • * iPSCs from affected individuals showed reduced MSL2 levels and changes in gene expression, leading to the characterization of a new MSL2-related disorder with unique clinical markers and a specific DNA episignature for diagnosis.
View Article and Find Full Text PDF

Chung-Jansen syndrome is a neurodevelopmental disorder characterized by intellectual disability, behavioral problems, obesity and dysmorphic features. It is caused by pathogenic variants in the PHIP gene that encodes for the Pleckstrin homology domain-interacting protein, which is part of an epigenetic modifier protein complex. Therefore, we hypothesized that PHIP haploinsufficiency may impact genome-wide DNA methylation (DNAm).

View Article and Find Full Text PDF
Article Synopsis
  • The study investigates the use of genomic DNA methylation analysis, or episignature profiling, in diagnosing neurodevelopmental disorders (NDDs) by evaluating two cohorts of patients: one with known pathogenic variants and another with uncertain mutations.
  • In the validation group of 59 patients, 90% exhibited expected episignatures, although some variants displayed overlapping profiles due to similar clinical symptoms.
  • In the test cohort of 38 patients, five cases identified novel pathogenic variants and confirmed diagnoses for conditions such as Cornelia de Lange syndrome, highlighting the potential of episignature analysis to tackle complex genetic diagnosis challenges.
View Article and Find Full Text PDF
Article Synopsis
  • CREB-binding protein (CBP) and E1A-associated protein (p300) are crucial for histone acetylation and gene regulation; mutations in these proteins lead to conditions like Rubinstein-Taybi syndrome (RSTS) and Menke-Hennekam syndrome (MKHK).
  • A study on 82 individuals with CBP/p300 variants revealed distinct phenotypes and identified three subtypes of MKHK based on specific protein domains (ZZ, TAZ2, and ID4), rather than the genes themselves.
  • DNA methylation profiles showed characteristic patterns associated with the different protein domains, allowing for better classification and understanding of the molecular mechanisms behind these syndromes.
View Article and Find Full Text PDF
Article Synopsis
  • Neurodevelopmental disorders (NDDs) stem from brain development issues, and research identifies loss-of-function (LoF) variations in the ZFHX3 gene as a cause of syndromic intellectual disability (ID).
  • A study of 42 individuals shows that variants in ZFHX3 lead to diverse symptoms like intellectual disability, autism spectrum disorder, distinct facial features, and developmental delays.
  • ZFHX3 plays a vital role in brain development, influences gene expression related to the nervous system, and has specific DNA methylation patterns linked to its function.
View Article and Find Full Text PDF

A PHP Error was encountered

Severity: Warning

Message: fopen(/var/lib/php/sessions/ci_session0fhfus3kbrjetv2g54l1m3m2hnpg6auh): Failed to open stream: No space left on device

Filename: drivers/Session_files_driver.php

Line Number: 177

Backtrace:

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: session_start(): Failed to read session data: user (path: /var/lib/php/sessions)

Filename: Session/Session.php

Line Number: 137

Backtrace:

File: /var/www/html/index.php
Line: 316
Function: require_once