Tjitske Kleefstra

MetaDome now supports GRCh38 alongside GRCh37, adds coordinate lookup, and identifies 52,463 GRCh38 ClinVar missense variants of uncertain significance with uncontradicted pathogenic evidence at homologous Pfam-domain positions.

SysNDD is a curated database of gene-disease associations for neurodevelopmental disorders, providing standardized evidence and annotations for 4,275 entities from 4,932 publications.

This study identifies EHMT1/G9a's role in sleep regulation through ROS homeostasis in insulin-producing cells, linking it to sleep disturbances in Kleefstra syndrome and common insomnia.

This study links metabolic vulnerability and sleep disturbances in Kleefstra syndrome using FDG-PET/CT imaging and Drosophila models.

The paper identifies de novo EHMT2 variants causing an autosomal dominant Kleefstra syndrome by impairing G9a methyltransferase activity, mimicking EHMT1 haploinsufficiency.

The paper identifies biallelic variants in RNU2-2 as a common cause of recessive neurodevelopmental disorders, showing higher prevalence than the dominant form in England.

The paper identifies WAPL as a novel cohesinopathy gene and driver of a genomic disorder, showing its role in developmental delay and other anomalies through clinical, in vitro, and in vivo analyses.

The paper develops MethaDory, a framework to train and validate DNAm-based classifiers for rare diseases using synthetic data, achieving high accuracy across multiple platforms.

The paper reanalyzes exome sequencing data from rare disease cases to identify previously undetected copy number variants, resulting in diagnoses for 51 families and partial explanations for 34 individuals.

The paper identifies a de novo EHMT2 mutation causing a Kleefstra-like syndrome by reducing enzyme activity and altering epigenetic profiles.

PhenomAD-NDD aggregates comorbid phenotypic data from 51,227 pediatric NDD individuals to identify enriched symptoms and improve clinical understanding.

The paper identifies six rare de novo missense variants in WDR5 associated with neurodevelopmental disorders and highlights their impact on COMPASS family protein interactions.

PhenoScore quantifies phenotypic similarity using AI and HPO data to improve genetic variant interpretation and genotype-phenotype studies.

This study identifies ANKRD11 missense variants as a cause of KBG syndrome by impairing protein stability or transcriptional activity, supporting haploinsufficiency as the underlying mechanism.

This study characterizes 29 individuals with FOXP2 variants, showing high prevalence of speech disorders and language impairments, with relatively specific phenotypes compared to other monogenic conditions.

This study shows that SETD1A loss-of-function mutations increase dendritic complexity and neuronal bursting in human neurons via a hyperactive cAMP/PKA pathway, which can be rescued by pharmacological intervention.

The paper shows inherited CHD3 variants cause Snijders Blok-Campeau syndrome with variable expressivity, overlapping with de novo variants' phenotypes, and suggests reduced penetrance is not due to expression compensation.

This study expands the known genotype and phenotype spectrum of SYT1-associated neurodevelopmental disorder by analyzing 22 individuals with de novo missense variants.

The paper benchmarks MEA recordings from healthy hiPSC-derived neuronal networks to establish standards for experimental design and analysis, showing MEAs are robust for disease-phenotyping and drug discovery.

This study investigates how KMT2D mutations in Kabuki Syndrome disrupt neuronal function through chromatin and transcriptional changes, independent of H3K4me1.

The paper identifies mutation-specific pathophysiological mechanisms in SATB1 variants causing distinct neurodevelopmental disorders.

This study characterizes SETD1A haploinsufficiency in humans and Drosophila, identifying a novel neurodevelopmental syndrome with cognitive and developmental symptoms.

The paper investigates how mutations in distinct genes causing intellectual disability and autism affect neuronal network development, finding shared effects on excitability and synaptic function.

This study shows that EHMT1 deficiency in human neurons leads to NMDAR hyperfunction, causing neuronal network dysfunction in Kleefstra syndrome, and demonstrates pharmacological rescue of these phenotypes.

The paper identifies de novo epigenetic variations in congenital disorders and shows their impact on gene expression and potential diagnostic relevance.

This study identifies 10 novel candidate genes for intellectual disability through a meta-analysis of de novo mutations from 2,104 trios.