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During translation, stop codon read-through occasionally happens when the stop codon is misread, skipped, or mutated, resulting in the production of aberrant proteins with C-terminal extension. These extended proteins are potentially deleterious, but their regulation is poorly understood. Here we show in vitro and in vivo evidence that mouse cFLIP-L with a 46-amino acid extension encoded by a read-through mutant gene is rapidly degraded by the ubiquitin-proteasome system, causing hepatocyte apoptosis during embryogenesis. The extended peptide interacts with an E3 ubiquitin ligase, TRIM21, to induce ubiquitylation of the mutant protein. In humans, 20 read-through mutations are related to hereditary disorders, and extended peptides found in human PNPO and HSD3B2 similarly destabilize these proteins, involving TRIM21 for PNPO degradation. Our findings indicate that degradation of aberrant proteins with C-terminal extension encoded by read-through mutant genes is a mechanism for loss of function resulting in hereditary disorders. [ABSTRACT FROM AUTHOR]

We present a case of a large clival chordoma in a 54-year-old female with a past medical history of Turner's syndrome and a 1.5-year history of nasal congestion. The tumor was extending in the nasopharynx to both pterygopalatine fossae. An expanded endoscopic endonasal approach was selected. Stereotactic navigation was utilized. Bilateral transmaxillary approach with ethmoidectomy was performed, and a transclival corridor to the deepest portion of the tumor was created. The tumor was successfully dissected off the medial walls of the cavernous sinuses. Gross-macroscopic resection was achieved. Surgical reconstruction of the skull base comprised of a fat graft, fascia lata overlay, and dural sealant. Given the extensive nasal involvement by the tumor, a vascularized nasoseptal flap was not feasible. The patient had an unremarkable postoperative course. She underwent intensity-modulated radiation therapy (IMRT) radiotherapy 6 weeks later, and was seen in follow-up 6 months later, with no issues. The link to the video can be found at: https://youtu.be/4bnsEUtieAw. [ABSTRACT FROM AUTHOR]