Browsing by Author "Othman, Mohamed"

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    Complementation of hypersensitivity to DNA interstrand crosslinking agents demonstrates that XRCC2 is a Fanconi anaemia gene
    (BMJ Journals, 2016-10) Park, Jung-Young; Virts, Elizabeth L.; Jankowska, Anna; Wiek, Constanze; Othman, Mohamed; Chakraborty, Sujata C.; Vance, Gail H.; Alkuraya, Fowzan S.; Hanenberg, Helmut; Andreassen, Paul R.; Medical and Molecular Genetics, School of Medicine
    Background Fanconi anemia (FA) is a heterogeneous inherited disorder clinically characterized by progressive bone marrow failure, congenital anomalies, and a predisposition to malignancies. Objective Determine, based on correction of cellular phenotypes, whether XRCC2 is a FA gene. Methods Cells (900677) from a previously identified patient with biallelic mutation of XRCC2, among other mutations, were genetically complemented with wild-type XRCC2. Results Wild-type XRCC2 corrects each of three phenotypes characteristic of FA cells, all related to the repair of DNA interstrand crosslinks, including increased sensitivity to mitomycin C (MMC), chromosome breakage, and G2-M accumulation in the cell cycle. Further, the p.R215X mutant of XRCC2, which is harbored by the patient, is unstable. This provides an explanation for the pathogenesis of this mutant, as does the fact that 900677 cells have reduced levels of other proteins in the XRCC2-RAD51B-C-D complex. Also, FANCD2 monoubiquitination and foci formation, but not assembly of RAD51 foci, are normal in 900677 cells. Thus, XRCC2 acts late in the FA-BRCA pathway as also suggested by hypersensitivity of 900677 cells to ionizing radiation. These cells also share milder sensitivities toward olaparib and formaldehyde with certain other FA cells. Conclusions XRCC2/FANCU is a FA gene, as is another RAD51 paralog gene, RAD51C/FANCO. Notably, similar to a subset of FA genes that act downstream of FANCD2, biallelic mutation of XRCC2/FANCU has not been associated with bone marrow failure. Taken together, our results yield important insights into phenotypes related to FA and its genetic origins.
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    Per-Oral Endoscopic Myotomy for Esophagogastric Junction Outflow Obstruction: A Multicenter Pilot Study
    (Elsevier, 2020) Jacobs, Chelsea C.; Perbtani, Yaseen; Yang, Dennis; Al-Haddad, Mohammad A.; Obaitan, Ite; Othman, Mohamed; Groth, Shawn; Sethi, Amrita; Agarunov, Emil; Repici, Alessandro; Maselli, Roberta; Galtieri, Alessia; Moremen, Jacob; Jenkins, Haley N.; Samarasena, Jason B.; Chang, Kenneth J.; Draganov, Peter V.; Medicine, School of Medicine