Genetics, Gene Therapy & Genetic Disease
Single variant, yet “double trouble”: TSC and KBG syndrome because of a large de novo inversionShort-read genome sequencing identified an 87-Mb inversion in a patient with atypical Tuberous sclerosis. The inversion disrupts TSC2 and ANKRD11, resulting in dual diagnosis of TSC/KBG syndromes.
Reduced myeloid commitment and increased uptake by macrophages of stem cell–derived HPS2 neutrophilsOur current work uses iPSC-derived neutrophils to unveil novel reasons for the neutropenia found in HPS2 patients. HPS2 iPSC-derived neutrophils have lower myeloid commitment, and are actively phagocytosed by macrophages present in the iPSC cultures or healthy donor macrophages.
CLN3 deficiency leads to neurological and metabolic perturbations during early developmentCln3 CRISPR mutant zebrafish larvae display BMP depletion and accumulation of glycerophosphodiesters and cholesteryl esters at very early developmental stages, recapitulating key features of human CLN3 disease.
USP27X variants underlying X-linked intellectual disability disrupt protein function via distinct mechanismsThis study uncovers mechanisms by which X-linked intellectual disability disorder 105 (#300984; OMIM) variants alter USP27X biology and function.
Analysis of the indispensable RAD51 cofactor BRCA2 in Naganishia liquefaciens, a Basidiomycota yeastIdentification of the BRCA2 homolog in the Basidiomycota yeast Naganishia liquefaciens reveals the general attributes of fungal BRCA2 and its essential role in Rad51-mediated homologous recombination.
Intrinsic deletion at 10q23.31, including the PTEN gene locus, is aggravated upon CRISPR-Cas9–mediated genome engineering in HAP1 cells mimicking cancer profilesThe unintended 10q23.31 deletion frequency rises in HAP1 cells stressed during CRISPR-Cas9 engineering, leading to aberrant molecular and cellular changes resembling common cancer patient deletions.
DOCK1 insufficiency disrupts trophoblast function and pregnancy outcomes via DUSP4-ERK pathwayThis study reveals that decreased DOCK1 in placental villi affects trophoblast function via the DUSP4-ERK pathway, providing insights into adverse pregnancy outcomes.
Meta-analysis of dispensable essential genes and their interactions with bypass suppressorsThis work compiles data from several studies on dispensable essential genes in S. cerevisiae to comprehensively characterize these genes and to explore how their interactions with bypass suppressor genes reflect evolution in natural populations.
Exploring the basis of heterogeneity of cancer aggressiveness among the mutated POLE variantsMechanisms and consequences of POLE mutations in human cancers.
Role of ciliopathy protein TMEM107 in eye development: insights from a mouse model and retinal organoidTMEM107 plays a crucial role in early vertebrate eye development and ciliogenesis in the differentiating retina, and its absence leads to eye defects and impaired retinal organoid formation.