Jul 2026· Human Molecular Genetics· Vol 35 16· 0 citations
Medicine
TL;DR
Combined transcriptomics profiling in cyp2u1-/- zebrafish and SPG56 patient iPSC-derived cortical neurons supports impaired neural network development as a key disease mechanism.
Findings strongly suggest that altered mitochondrial morphology in DRP1 mutant neurons leads to pathogenic dysregulation of synaptic development and activity.
T. Baum, J. Costanzo, C. Bodnya et al.· Journal of Neurodevelopmenta...· 0 citations
The findings implicate DCLK1 in a previously unrecognized progressive neurodevelopmental disorder and demonstrate the power of integrative cross-species functional genomics in resolving ultra-rare disease variants.
Stephen C. Pak, David Butler, Wei-Xi Yuan et al.· Research Square· 0 citations
This study provides substantial evidence for the vital role of trip12 in the early stages of development, as homozygous individuals exhibited early mortality by Day 23 post-fertilization, while a substantial mortality rate was observed by Day 35 in ‘heterozygous’ mutants.
Maider Roibás-Santos, P. Suarez‐Bregua, J. Rotllant et al.· Brain Communications· 0 citations
The biological plausibility of LNX2 as a candidate gene for neurodevelopmental disorders is supported, highlighting its preferential association with neuronal projection-cell networks, synaptic vesicle trafficking pathways, and neuron-specific regulatory programs.
M. Vinci, M. Figura, A. Musumeci et al.· Genes· 0 citations
Variants in BRSK2, encoding brain specific kinase-2, have recently been associated with an autosomal dominant neurodevelopmental disorder (NDD). We have assembled 52 cases with heterozygous BRSK2 variants and variable neurodevelopmental phenotypes with frequent neuropsychiatric and behavioral symptoms. The variant spectrum included 15 different truncating variants, seven (potential) splice variants, three structural variants, and 12 different missense variants. Of the missense variants, seven were in the kinase domain, and the others in the UBA and the KA1 domain or outside domains. Variants occurred de novo in 19 cases and were inherited in 18. We utilized Drosophila melanogaster as a model and assessed viability and performed climbing and bang sensitivity assays upon knockdown of the fly orthologue sff or upon overexpression of wildtype or mutant human BRSK2. Pan-neuronal knockdown of sff resulted in impaired locomotor behavior and seizure susceptibility. Ubiquitous or pan-neuronal overexpression of human wildtype BRSK2 in Drosophila resulted in lethality or locomotor impairment, respectively, indicating toxicity. Overexpressing mutant BRSK2 did not or incompletely affect viability and locomotor behavior for six of seven tested kinase domain missense variants and one KA1 domain variant, indicating a (partial) loss-of-function effect. Interestingly, overexpressing BRSK2 with the remaining missense variant from the kinase domain and the two most C-terminal missense variants resulted in possible gain of function. Our findings further delineate the clinical and molecular spectrum of BRSK2-associated NDD and provide further insights into the role of BRSK2/sff in nervous system function and dysfunction.
Palak Singhal, Tzung-Chien Hsieh, Nadja Ehmke et al.· European Journal of Human Ge...· 0 citations
The integrated analysis establishes the first cross-species model for GNB1E, suggests common neurological mechanisms and molecular pathways linked to GNB1E, and provides a framework for mechanistic and therapeutic studies.
Haritha P. Reddy, Vigneshwar Ranjan, Merav Klo et al.· bioRxiv· 1 citation