Publications by authors named "H C A Lammertse"
Article Synopsis
- The study investigates a neurodevelopmental disorder (-RD) caused by mutations in the MUNC18-1 gene, leading to symptoms like developmental delay and seizures, with varying severity among patients.
- Using advanced techniques, researchers analyzed neurons derived from patients' stem cells, finding reduced levels of the MUNC18-1 protein, along with dysregulated proteins linked to synapse function and altered neuronal network activity.
- The findings reveal common cellular traits across patients with -RD while also highlighting distinct phenotypic differences, suggesting varied underlying mechanisms of the disorder that could inform future research and therapy development.
Article Synopsis
- Induced pluripotent stem cells (iPSCs) are increasingly used for modeling brain disorders, but there's a lack of clarity on the best study designs and statistical analyses.
- The researchers compared different study designs, generating various types of data from iPSC-derived neurons, and found that many existing studies are underpowered.
- They discovered that using isogenic iPSC lines offers more statistical power compared to traditional case-control designs and introduced a free online tool to help researchers optimize study designs based on preliminary data.
Absence of presynaptic protein MUNC18-1 (gene: ) leads to neuronal cell death at an immature stage before synapse formation. Here, we performed transcriptomic and proteomic profiling of immature knockout (KO) cells to discover which cellular processes depend on MUNC18-1. Hippocampi of KO mice showed cell-type specific dysregulation of 2123 transcripts primarily related to synaptic transmission and immune response.
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- * In Stxbp1 null mutants, dynamin-1 levels drop significantly, and the transcript levels of its encoding gene, Dnm1, are also reduced by 50%, impacting several other endocytic proteins to a lesser degree.
- * The study indicates that MUNC18-1 does not directly bind dynamin-1, and reducing dynamin-1 alone doesn’t cause neurodegeneration in Stxbp1 mutants, suggesting that MUNC18-1
Article Synopsis
- * A majority of participants exhibit neurodevelopmental issues (95%) and seizures (89%), with common seizure types and early onset, underscoring the severity of STXBP1-related conditions.
- * Despite identifying frequent genetic variants, no specific associations were found between these variants and particular clinical syndromes, indicating a high level of variability in the clinical presentation of STXBP1-related disorders.