Tjakko J. van Ham

MetaDome 2027: a comprehensively updated resource for aggregating missense variant evidence across homologous human protein domains

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.

BLOC1S1 variants cause lysosomal and autophagic defects resulting in a hypomyelinating leukodystrophy with epileptic encephalopathy

This study identifies BLOC1S1 variants causing a hypomyelinating leukodystrophy with epileptic encephalopathy, showing impaired lysosomal and autophagic function.

TFEB-depletion rescues TMEM106B-related myelin defects in zebrafish

This study shows that TMEM106B affects myelination through a TFEB-dependent pathway in zebrafish, and TFEB inhibition rescues myelin defects caused by TMEM106B mutations.

Long-read DNA and RNA sequencing reveal an intronic retrotransposon insertion in TCOF1 causing Treacher Collins syndrome

Synthetic epigenomes for open cross-platform episignature classifiers

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.

Bi-allelic variants in the aminopeptidase XPNPEP3 cause mitochondrial disease with pediatric cardiomyopathy

This study identifies bi-allelic XPNPEP3 variants causing mitochondrial disease with pediatric cardiomyopathy, revealing impaired mitochondrial protein processing as the underlying mechanism.

The non-canonical thioreductase TMX2 is essential for neuronal survival during embryonic brain development

This study shows TMX2 is essential for newborn neuron survival during zebrafish embryonic brain development, with loss causing rapid cell death and calcium dysregulation.

RNA-sequencing improves diagnosis for neurodevelopmental disorders by identifying pathogenic non-coding variants and reinterpretation of coding variants

This study uses RNA-seq to improve diagnosis of neurodevelopmental disorders by identifying non-coding variants and reinterpreting coding variants, increasing diagnostic yield by 12%.

Colony stimulating factor 1 signaling regulates myeloid fates in zebrafish via distinct action of its receptors and ligands

This study investigates the roles of Csf1rs and their ligands in zebrafish myelopoiesis, revealing distinct functions in macrophage and granulocyte differentiation.

Comprehensive multi-omics integration identifies differentially active enhancers during human brain development with clinical relevance

The paper identifies 39,709 differentially active enhancers in human fetal brain development linked to neurodevelopmental disorders and GWAS loci.

Myelin biogenesis is associated with pathological ultrastructure that is resolved by microglia during development

The paper investigates myelin structural changes during development in mice and zebrafish, finding that myelin degeneration is resolved by microglia, while sheath retractions occur independently.

Zebrafish macrophage developmental arrest underlies depletion of microglia and reveals Csf1r-independent metaphocytes

The paper studies macrophage development in zebrafish lacking CSF1R, finding developmental arrest and the emergence of Csf1r-independent metaphocytes.

Loss of UGP2 in brain leads to a severe epileptic encephalopathy, emphasizing that bi-allelic isoform specific start-loss mutations of essential genes can cause genetic diseases

The paper identifies a recurrent start codon mutation in UGP2 causing a severe epileptic encephalopathy, showing that isoform-specific expression loss of an essential gene can lead to disease.

Reverse genetic screen reveals that Il34 facilitates yolk sac macrophage distribution and seeding of the brain

The paper uses a CRISPR/Cas9 screen in zebrafish to identify Il34 as a factor facilitating yolk sac macrophage distribution and brain colonization.

Dynamic control of proinflammatory cytokines Il-1β and Tnf-α by macrophages is necessary for functional spinal cord regeneration in zebrafish

The paper shows that macrophage-mediated dynamic control of Il-1β and Tnf-α is essential for spinal cord regeneration in zebrafish.