De Novo Truncating Variants in SON Cause Intellectual Disability, Congenital Malformations, and Failure to Thrive Mari J. Tokita, Alicia A. Braxton,

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De Novo Truncating Variants in SON Cause Intellectual Disability, Congenital Malformations, and Failure to Thrive Mari J. Tokita, Alicia A. Braxton, Yunru Shao, Andrea M. Lewis, Marie Vincent, Sébastien Küry, Thomas Besnard, Bertrand Isidor, Xénia Latypova, Stéphane Bézieau, Pengfei Liu, Connie S. Motter, Catherine Ward Melver, Nathaniel H. Robin, Elena M. Infante, Marianne McGuire, Areeg El-Gharbawy, Rebecca O. Littlejohn, Scott D. McLean, Weimin Bi, Carlos A. Bacino, Seema R. Lalani, Daryl A. Scott, Christine M. Eng, Yaping Yang, Christian P. Schaaf, Magdalena A. Walkiewicz The American Journal of Human Genetics Volume 99, Issue 3, Pages 720-727 (September 2016) DOI: 10.1016/j.ajhg.2016.06.035 Copyright © 2016 American Society of Human Genetics Terms and Conditions

Figure 1 Photographs and Pedigrees of Subjects with SON Variants Photographs show subjects reported in this article, and pedigrees illustrate the de novo status of all detected SON variants. Shaded symbols represent affected individuals. The American Journal of Human Genetics 2016 99, 720-727DOI: (10.1016/j.ajhg.2016.06.035) Copyright © 2016 American Society of Human Genetics Terms and Conditions

Figure 2 Intragenic Location of SON Variants and Key Protein Functional Domains (A) All but one of the SON variants in the described individuals localize to exon 3 of SON (GenBank: NM_138927.2). (B) Approximate location of amino acid changes in relation to SON’s key functional domains, which include a unique central highly repetitive region, an RS-rich domain, a G-patch domain, and a double-stranded RNA-binding motif (DSRM). Data were extracted from GenBank: NP_620305.2. This panel was adapted from Hickey et al.4 The American Journal of Human Genetics 2016 99, 720-727DOI: (10.1016/j.ajhg.2016.06.035) Copyright © 2016 American Society of Human Genetics Terms and Conditions