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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, J effrey 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
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:
It is part of: Genetics in Medicine, 2020, vol. 22, num. 7, p. 1215-1226
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ISSN: 1098-3600
Appears in Collections:Articles publicats en revistes (Genètica, Microbiologia i Estadística)

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