Chromosome engineering to correct a complex rearrangement on Chromosome 8 reveals the effects of 8p syndrome on gene expression and neural differentiation
Chromosomal rearrangements on the short arm of Chromosome 8 cause 8p syndrome, a rare developmental disorder characterized by neurodevelopmental delays, epilepsy, and cardiac abnormalities. Although significant progress has been made
in managing the symptoms of 8p syndrome and other conditions caused by large-scale chromosomal aneuploidies, no therapeutic approach has yet been demonstrated to target the underlying disease-causing chromosome. Here, we establish a
two-step approach to eliminate the abnormal copy of Chromosome 8 and restore euploidy in cells derived from an individual with a complex rearrangement of Chromosome 8p. Transcriptomic analysis revealed 361 differentially expressed
genes between the proband and the euploid revertant, highlighting genes both within and outside the 8p region that
may contribute to 8p syndrome pathology. Furthermore, we demonstrate that the proband exhibits a significant defect
in neural differentiation that could be partially rescued by treatment with small-molecule inhibitors of cell death. Our
work demonstrates the feasibility of using chromosome engineering to correct complex aneuploidies in vitro and establishes
a platform to further dissect the pathophysiology of 8p syndrome and other conditions caused by chromosomal
rearrangements
Evaluation of epilepsy in 8p-related disorders
8p-related disorders are genetic conditions associated with chromosomal rearrangements on the short arm of chromosome 8. This study aimed to characterize the epilepsy phenotype in patients with 8p-related disorders..
Chromosome 8p Syndromes Clinical Presentation and Management Guidelines
The p-arm of chromosome 8 is home to repeating Olfactory Receptor gene clusters known as Low Copy Repeat regions
Chromosome engineering to restore euploidy in cells harboring a complex rearrangement of chromosome 8
Chromosomal rearrangements on the short arm of chromosome 8 cause 8p syndrome, a rare developmental disorder characterized by neurodevelopmental delays….
Clinical and Genomic Characterization of 8p Cytogenomic Disorders
To provide a detailed clinical and cytogenomic summary of individuals with chromosome 8p rearrangements of invdupdel(8p), del(8p), and dup(8p).
