Universität zu Köln

Tokita, Mari J., Chen, Chun-An, Chitayat, David, Macnamara, Ellen ORCID: 0000-0002-9418-3287, Rosenfeld, Jill A., Hanchard, Neil, Lewis, Andrea M., Brown, Chester W., Marom, Ronit ORCID: 0000-0003-3524-661X, Shao, Yunru, Novacic, Danica, Wolfe, Lynne, Wahl, Colleen, Tifft, Cynthia J., Toro, Camilo, Bernstein, Jonathan A., Hale, Caitlin L., Silver, Julia, Hudgins, Louanne, Ananth, Amitha, Hanson-Kahn, Andrea, Shuster, Shirley, Magoulas, Pilar L., Patel, Vipulkumar N., Zhu, Wenmiao, Chen, Stella M., Jiang, Yanjun, Liu, Pengfei ORCID: 0000-0002-4177-709X, Eng, Christine M., Batkovskyte, Dominyka, di Ronza, Alberto, Sardiello, Marco, Lee, Brendan H., Schaaf, Christian P., Yang, Yaping and Wang, Xia ORCID: 0000-0002-7750-1167 (2018). De Novo Missense Variants in TRAF7 Cause Developmental Delay, Congenital Anomalies, and Dysmorphic Features. Am. J. Hum. Genet., 103 (1). S. 154 - 163. CAMBRIDGE: CELL PRESS. ISSN 1537-6605

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Abstract

TRAF7 is a multi-functional protein involved in diverse signaling pathways and cellular processes. The phenotypic consequence of germ-line TRAF7 variants remains unclear. Here we report missense variants in TRAF7 in seven unrelated individuals referred for clinical exome sequencing. The seven individuals share substantial phenotypic overlap, with developmental delay, congenital heart defects, limb and digital anomalies, and dysmorphic features emerging as key unifying features. The identified variants are de novo in six individuals and comprise four distinct missense changes, including a c.1964G>A (p.Arg655Gln) variant that is recurrent in four individuals. These variants affect evolutionarily conserved amino acids and are located in key functional domains. Gene-specific mutation rate analysis showed that the occurrence of the de novo variants in TRAF7 (p = 2.6 x 10(-3)) and the recurrent de novo c.1964G>A (p.Arg655Gln) variant (p = 1.9 x 10(-8)) in our exome cohort was unlikely to have occurred by chance. In vitro analyses of the observed TRAF7 mutations showed reduced ERK1/2 phosphorylation. Our findings suggest that missense mutations in TRAF7 are associated with a multisystem disorder and provide evidence of a role for TRAF7 in human development.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Tokita, Mari J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Chen, Chun-An UNSPECIFIED UNSPECIFIED UNSPECIFIED Chitayat, David UNSPECIFIED UNSPECIFIED UNSPECIFIED Macnamara, Ellen UNSPECIFIED orcid.org/0000-0002-9418-3287 UNSPECIFIED Rosenfeld, Jill A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hanchard, Neil UNSPECIFIED UNSPECIFIED UNSPECIFIED Lewis, Andrea M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Brown, Chester W. UNSPECIFIED UNSPECIFIED UNSPECIFIED Marom, Ronit UNSPECIFIED orcid.org/0000-0003-3524-661X UNSPECIFIED Shao, Yunru UNSPECIFIED UNSPECIFIED UNSPECIFIED Novacic, Danica UNSPECIFIED UNSPECIFIED UNSPECIFIED Wolfe, Lynne UNSPECIFIED UNSPECIFIED UNSPECIFIED Wahl, Colleen UNSPECIFIED UNSPECIFIED UNSPECIFIED Tifft, Cynthia J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Toro, Camilo UNSPECIFIED UNSPECIFIED UNSPECIFIED Bernstein, Jonathan A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hale, Caitlin L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Silver, Julia UNSPECIFIED UNSPECIFIED UNSPECIFIED Hudgins, Louanne UNSPECIFIED UNSPECIFIED UNSPECIFIED Ananth, Amitha UNSPECIFIED UNSPECIFIED UNSPECIFIED Hanson-Kahn, Andrea UNSPECIFIED UNSPECIFIED UNSPECIFIED Shuster, Shirley UNSPECIFIED UNSPECIFIED UNSPECIFIED Magoulas, Pilar L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Patel, Vipulkumar N. UNSPECIFIED UNSPECIFIED UNSPECIFIED Zhu, Wenmiao UNSPECIFIED UNSPECIFIED UNSPECIFIED Chen, Stella M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Jiang, Yanjun UNSPECIFIED UNSPECIFIED UNSPECIFIED Liu, Pengfei UNSPECIFIED orcid.org/0000-0002-4177-709X UNSPECIFIED Eng, Christine M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Batkovskyte, Dominyka UNSPECIFIED UNSPECIFIED UNSPECIFIED di Ronza, Alberto UNSPECIFIED UNSPECIFIED UNSPECIFIED Sardiello, Marco UNSPECIFIED UNSPECIFIED UNSPECIFIED Lee, Brendan H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schaaf, Christian P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Yang, Yaping UNSPECIFIED UNSPECIFIED UNSPECIFIED Wang, Xia UNSPECIFIED orcid.org/0000-0002-7750-1167 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-179915
DOI:	10.1016/j.ajhg.2018.06.005
Journal or Publication Title:	Am. J. Hum. Genet.
Volume:	103
Number:	1
Page Range:	S. 154 - 163
Date:	2018
Publisher:	CELL PRESS
Place of Publication:	CAMBRIDGE
ISSN:	1537-6605
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MUTATIONS; PTPN11; BRCA2 Multiple languages Genetics & Heredity Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/17991