دورية أكاديمية
Biallelic MAD2L1BP (p31comet) mutation is associated with mosaic aneuploidy and juvenile granulosa cell tumors
| العنوان: | Biallelic MAD2L1BP (p31comet) mutation is associated with mosaic aneuploidy and juvenile granulosa cell tumors |
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| المؤلفون: | Ghada M. H. Abdel-Salam, Susanne Hellmuth, Elise Gradhand, Stephan Käseberg, Jennifer Winter, Ann-Sophie Pabst, Maha M. Eid, Holger Thiele, Peter Nürnberg, Birgit S. Budde, Mohammad Reza Toliat, Ines B. Brecht, Christopher Schroeder, Axel Gschwind, Stephan Ossowski, Friederike Häuser, Heidi Rossmann, Mohamed S. Abdel-Hamid, Ibrahim Hegazy, Ahmed G. Mohamed, Dominik T. Schneider, Aida Bertoli-Avella, Peter Bauer, Jillian N. Pearring, Rolph Pfundt, Alexander Hoischen, Christian Gilissen, Dennis Strand, Ulrich Zechner, Soha A. Tashkandi, Eissa A. Faqeih, Olaf Stemmann, Susanne Strand, Hanno J. Bolz |
| المصدر: | JCI Insight, Vol 8, Iss 22 (2023) |
| بيانات النشر: | American Society for Clinical investigation |
| سنة النشر: | 2023 |
| المجموعة: | Directory of Open Access Journals: DOAJ Articles |
| مصطلحات موضوعية: | Genetics, Oncology, Medicine |
| الوصف: | MAD2L1BP-encoded p31comet mediates Trip13-dependent disassembly of Mad2- and Rev7-containing complexes and, through this antagonism, promotes timely spindle assembly checkpoint (SAC) silencing, faithful chromosome segregation, insulin signaling, and homology-directed repair (HDR) of DNA double-strand breaks. We identified a homozygous MAD2L1BP nonsense variant, R253*, in 2 siblings with microcephaly, epileptic encephalopathy, and juvenile granulosa cell tumors of ovary and testis. Patient-derived cells exhibited high-grade mosaic variegated aneuploidy, slowed-down proliferation, and instability of truncated p31comet mRNA and protein. Corresponding recombinant p31comet was defective in Trip13, Mad2, and Rev7 binding and unable to support SAC silencing or HDR. Furthermore, C-terminal truncation abrogated an identified interaction of p31comet with tp53. Another homozygous truncation, R227*, detected in an early-deceased patient with low-level aneuploidy, severe epileptic encephalopathy, and frequent blood glucose elevations, likely corresponds to complete loss of function, as in Mad2l1bp–/– mice. Thus, human mutations of p31comet are linked to aneuploidy and tumor predisposition. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 2379-3708 |
| العلاقة: | https://doi.org/10.1172/jci.insight.170079Test; https://doaj.org/toc/2379-3708Test; https://doaj.org/article/c2f7dbb684e54ea28e6d06a849f00507Test |
| الإتاحة: | https://doi.org/10.1172/jci.insight.170079Test https://doaj.org/article/c2f7dbb684e54ea28e6d06a849f00507Test |
| رقم الانضمام: | edsbas.9737E68C |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 23793708 |
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