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http://hdl.handle.net/2445/169433
Title: | Phenotypic spectrum and transcriptomic profile associated with germline variants in TRAF7 |
Author: | Castilla-Vallmanya, Laura Selmer, Kaja K. Dimartino, Clémantine Rabionet Janssen, Raquel Blanco-Sánchez, Bernardo Yang, Sandra Reijnders, Margot R. F. van Essen, Antoine J. Oufadem, Myriam Vigeland, Magnus D. Stadheim, Barbro Houge, Gunnar Cox, Helen Kingston, Helen Clayton-Smith, Jill Innis, Jeffrey W. Iascone, Maria Cereda, Anna Gabbiadini, Sara Chung, Wendy K. Sanders, Victoria Charrow, Joel Bryant, Emily Millichap, John Vitobello, Antonio Thauvin, Christel Mau-Them, Frederic Tran Faivre, Laurence Lesca, Gaetan Labalme, Audrey Rougeot, Christelle Chatron, Nicolas Sanlaville, Damien Christensen, Katherine M. Kirby, Amelia Lewandowski, Raymond Gannaway, Rachel Balcells Comas, Susana Grinberg Vaisman, Daniel Raúl Urreizti, Roser |
Keywords: | Fibroblasts Tumors Necrosi Fibroblasts Tumors Necrosis |
Issue Date: | 7-May-2020 |
Publisher: | American College of Medical Genetics and Genomics |
Abstract: | Purpose: Somatic variants in tumor necrosis factor receptor-associated factor 7 (TRAF7) cause meningioma, while germline variants have recently been identified in seven patients with developmental delay and cardiac, facial, and digital anomalies. We aimed to define the clinical and mutational spectrum associated with TRAF7 germline variants in a large series of patients, and to determine the molecular effects of the variants through transcriptomic analysis of patient fibroblasts. Methods: We performed exwct ome, targeted capture, and Sanger sequencing of patients with undiagnosed developmental disorders, in multiple independent diagnostic or research centers. Phenotypic and mutational comparisons were facilitated through data exchange platforms. Whole-transcriptome sequencing was performed on RNA from patient- and control-derived fibroblasts. Results: We identified heterozygous missense variants in TRAF7 as the cause of a developmental delay-malformation syndrome in 45 patients. Major features include a recognizable facial gestalt (characterized in particular by blepharophimosis), short neck, pectus carinatum, digital deviations, and patent ductus arteriosus. Almost all variants occur in the WD40 repeats and most are recurrent. Several differentially expressed genes were identified in patient fibroblasts. Conclusion: We provide the first large-scale analysis of the clinical and mutational spectrum associated with the TRAF7 developmental syndrome, and we shed light on its molecular etiology through transcriptome studies. |
Note: | Versió postprint del document publicat a: https://doi.org/10.1038/s41436-020-0792-7 |
It is part of: | Genetics in Medicine, 2020, vol. 22, num. 7, p. 1215-1226 |
URI: | http://hdl.handle.net/2445/169433 |
Related resource: | https://doi.org/10.1038/s41436-020-0792-7 |
ISSN: | 1098-3600 |
Appears in Collections: | Articles publicats en revistes (Genètica, Microbiologia i Estadística) |
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699023.pdf | 3.58 MB | Adobe PDF | View/Open |
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