{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T07:57:08Z","timestamp":1768291028426,"version":"3.49.0"},"reference-count":29,"publisher":"Cold Spring Harbor Laboratory","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cold Spring Harb Mol Case Stud"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:p>Chung\u2013Jansen syndrome (CJS) is a rare, autosomal dominant disorder characterized by developmental delay, intellectual disability\/cognitive impairment, behavioral challenges, obesity, and dysmorphic features. CJS is associated with heterozygous variants in <jats:italic>PHIP<\/jats:italic> (Pleckstrin-Homology Interacting Protein), a gene that encodes one of several substrate receptors for Cullin4-RING (CRL4) E3 ubiquitin ligase complex. Full-length PHIP, also called DCAF14, was recently identified to function as a replication stress response protein. Herein, we report the identification of two <jats:italic>PHIP<\/jats:italic> missense variants identified by exome sequencing in unrelated individuals with CJS. The variants p.D488V and p.E963G occur in different functional elements of DCAF14-WD40 repeat domain and pleckstrin homology-binding region (PBR), respectively. Using DNA fiber assays, we reveal that cells expressing either variant exhibit defective replication fork progression in conditions of replication stress. Furthermore, unlike wild-type DCAF14, both variants fail to accomplish DNA replication after exposure to genotoxic stress indicating a critical role of DCAF14 in protecting stalled replication forks. Thus, we have identified replication defects associated with CJS variants and predict replication-associated genome instability with CJS syndrome.<\/jats:p>","DOI":"10.1101\/mcs.a006212","type":"journal-article","created":{"date-parts":[[2022,7,21]],"date-time":"2022-07-21T20:10:10Z","timestamp":1658434210000},"page":"a006212","source":"Crossref","is-referenced-by-count":6,"title":["<i>PHIP<\/i> variants associated with Chung\u2013Jansen syndrome disrupt replication fork stability and genome integrity"],"prefix":"10.1101","volume":"8","author":[{"given":"Neysha","family":"Tirado-Class","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caitlin","family":"Hathaway","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wendy 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