PRDM10 directs FLCN expression in a novel disorder overlapping with Birt-Hogg-Dubé syndrome and familial lipomatosis
| العنوان: | PRDM10 directs FLCN expression in a novel disorder overlapping with Birt-Hogg-Dubé syndrome and familial lipomatosis |
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| المؤلفون: | Irma van de Beek, Iris E Glykofridis, Jan C Oosterwijk, Peter C van den Akker, Gilles F H Diercks, Maria C Bolling, Quinten Waisfisz, Arjen R Mensenkamp, Jesper A Balk, Rob Zwart, Alex V Postma, Hanne E J Meijers-Heijboer, R Jeroen A van Moorselaar, Rob M F Wolthuis, Arjan C Houweling |
| المساهمون: | Targeted Gynaecologic Oncology (TARGON), Damage and Repair in Cancer Development and Cancer Treatment (DARE), Translational Immunology Groningen (TRIGR), Human Genetics, ACS - Heart failure & arrhythmias, Medical Biology, ACS - Pulmonary hypertension & thrombosis, ARD - Amsterdam Reproduction and Development, ACS - Amsterdam Cardiovascular Sciences, Human genetics, Cancer Center Amsterdam, CCA - Cancer biology and immunology, AII - Cancer immunology, Amsterdam Neuroscience - Complex Trait Genetics, CCA - Cancer Treatment and quality of life, Amsterdam Reproduction & Development (AR&D), Urology, CCA - Imaging and biomarkers, ACS - Atherosclerosis & ischemic syndromes |
| المصدر: | van de Beek, I, Glykofridis, I E, Oosterwijk, J C, van den Akker, P C, Diercks, G F H, Bolling, M C, Waisfisz, Q, Mensenkamp, A R, Balk, J A, Zwart, R, Postma, A V, Meijers-Heijboer, H E J, van Moorselaar, R J A, Wolthuis, R M F & Houweling, A C 2023, ' PRDM10 directs FLCN expression in a novel disorder overlapping with Birt-Hogg-Dubé syndrome and familial lipomatosis ', Human Molecular Genetics, vol. 32, no. 7, pp. 1223-1235 . https://doi.org/10.1093/hmg/ddac288 Human Molecular Genetics, 32, 1223-1235 Human Molecular Genetics, 32(7), 1223-1235. Oxford University Press Human molecular genetics, 32(7), 1223-1235. Oxford University Press Human Molecular Genetics, 32, 7, pp. 1223-1235 |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | All institutes and research themes of the Radboud University Medical Center, Women's cancers Radboud Institute for Molecular Life Sciences [Radboudumc 17], Genetics, General Medicine, Molecular Biology, Genetics (clinical) |
| الوصف: | Contains fulltext : 291515.pdf (Publisher’s version ) (Open Access) Birt-Hogg-Dubé syndrome (BHD) is an autosomal dominant disorder characterized by fibrofolliculomas, pulmonary cysts, pneumothoraces and renal cell carcinomas. Here, we reveal a novel hereditary disorder in a family with skin and mucosal lesions, extensive lipomatosis and renal cell carcinomas. The proband was initially diagnosed with BHD based on the presence of fibrofolliculomas, but no pathogenic germline variant was detected in FLCN, the gene associated with BHD. By whole exome sequencing we identified a heterozygous missense variant (p.(Cys677Tyr)) in a zinc-finger encoding domain of the PRDM10 gene which co-segregated with the phenotype in the family. We show that PRDM10Cys677Tyr loses affinity for a regulatory binding motif in the FLCN promoter, abrogating cellular FLCN mRNA and protein levels. Overexpressing inducible PRDM10Cys677Tyr in renal epithelial cells altered the transcription of multiple genes, showing overlap but also differences with the effects of knocking out FLCN. We propose that PRDM10 controls an extensive gene program and acts as a critical regulator of FLCN gene transcription in human cells. The germline variant PRDM10Cys677Tyr curtails cellular folliculin expression and underlies a distinguishable syndrome characterized by extensive lipomatosis, fibrofolliculomas and renal cell carcinomas. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 0964-6906 |
| DOI: | 10.1093/hmg/ddac288 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::19bee29415900ea2982a28cc3469f7db https://research.vumc.nl/en/publications/d755d70a-4c1f-4979-ab6b-f902c4942091 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....19bee29415900ea2982a28cc3469f7db |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 09646906 |
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| DOI: | 10.1093/hmg/ddac288 |