No abstract

Fanconi anemia (FA) is a rare inherited disorder clinically characterized by congenital malformations, progressive bone marrow failure and cancer susceptibility. At the cellular level, FA is associated with hypersensitivity to DNA-crosslinking genotoxins. Eight of 17 known FA genes assemble the FA E3 ligase complex, which catalyzes monoubiquitination of FANCD2 and is essential for replicative DNA crosslink repair. Here, we identify the first FA patient with biallelic germline mutations in the ubiquitin E2 conjugase UBE2T. Both mutations were aluY-mediated: a paternal deletion and maternal duplication of exons 2–6. These loss-of-function mutations in UBE2T induced a cellular phenotype similar to biallelic defects in early FA genes with the absence of FANCD2 monoubiquitination. The maternal duplication produced a mutant mRNA that could encode a functional protein but was degraded by nonsense-mediated mRNA decay. In the patient's hematopoietic stem cells, the maternal allele with the duplication of exons 2–6 spontaneously reverted to a wild-type allele by monoallelic recombination at the duplicated aluY repeat, thereby preventing bone marrow failure. Analysis of germline DNA of 814 normal individuals and 850 breast cancer patients for deletion or duplication of UBE2T exons 2–6 identified the deletion in only two controls, suggesting aluY-mediated recombinations within the UBE2T locus are rare and not associated with an increased breast cancer risk. Finally, a loss-of-function germline mutation in UBE2T was detected in a high-risk breast cancer patient with wild-type BRCA1/2. Cumulatively, we identified UBE2T as a bona fide FA gene (FANCT) that also may be a rare cancer susceptibility gene.

Although SCC with and without IP association are considered different diseases, their demographics and outcomes seem similar. Nodal metastasis was noted to be higher in the SCC cohort, which may indicate different tumor biology. Further study is warranted.

No abstract

Senior medical students are facing an unparalleled experiential gap left by COVID-19 restrictions. Due to a shared commitment to safety, equity, and well-being, away rotations are actively being discouraged or even prohibited. As a result, students transitioning to residency encounter reduced clinical training experiences and decreased access to advising, mentorship, and research opportunities. In addition, limited exposure to residency life across subspecialties and institutions poses unique challenges during the current residency application cycle. The otolaryngology–head and neck surgery community has met these unprecedented challenges by producing diverse electronic resources for specialty-specific clinical education, as well as discussing ways to increase access to advising. In this commentary, we review these initiatives and propose an institutional virtual event as a platform for meeting goals previously achieved by visiting subinternships.