Identifying key underlying regulatory networks and predicting targets of orphan C/D box SNORD116 snoRNAs in Prader-Willi syndrome.

Prader-Willi syndrome (PWS) is a rare neurodevelopmental disorder characterized by neonatal hypotonia, followed by hyperphagia and obesity. Most PWS cases exhibit megabase-scale deletions of paternally imprinted 15q11-q13 locus. However, several PWS patients have been identified harboring much smaller deletions encompassing the SNORD116 gene cluster, suggesting these genes are direct drivers of PWS phenotypes.

A NOTCH2 pathogenic variant and HES1 regulate osteoclastogenesis in induced pluripotent stem cells.

Hajdu Cheney Syndrome (HCS), a monogenic disorder associated with NOTCH2 pathogenic variants, presents with neurological, craniofacial and skeletal abnormalities. Mouse models of the disease exhibit osteopenia. To determine the consequences of a HCS pathogenic variant in human cells, induced pluripotent NCRM1 and NCRM5 stem (iPS) cells harboring a NOTCH2 mutation or null for HES1 alleles were created.

Generation of isogenic models of Angelman syndrome and Prader-Willi syndrome in CRISPR/Cas9-engineered human embryonic stem cells.

Angelman syndrome (AS) and Prader-Willi syndrome (PWS), two distinct neurodevelopmental disorders, result from loss of expression from imprinted genes in the chromosome 15q11-13 locus most commonly caused by a megabase-scale deletion on either the maternal or paternal allele, respectively. Each occurs at an approximate incidence of 1/15,000 to 1/30,000 live births and has a range of debilitating phenotypes. Patient-derived induced pluripotent stem cells (iPSCs) have been valuable tools to understand human-relevant gene regulation at this locus and have contributed to the development of therapeutic approaches for AS.