Expanding the Spectrum of BAF-Related Disorders: De Novo Variants in SMARCC2 Cause a Syndrome with Intellectual Disability and Developmental Delay

K Machol; J Rousseau; S Ehresmann; T Garcia; TTM Nguyen; RC Spillmann; JA Sullivan; V Shashi; YH Jiang; N Stong; E Fiala; M Willing; R Pfundt; T Kleefstra; MT Cho; H McLaughlin; M Rosello Piera; C Orellana; F Martínez; A Caro-Llopis; S Monfort; T Roscioli; CY Nixon; MF Buckley; A Turner; WD Jones; PM van Hasselt; FC Hofstede; KLI van Gassen; AS Brooks; MA van Slegtenhorst; K Lachlan; J Sebastian; S Madan-Khetarpal; D Sonal; N Sakkubai; J Thevenon; L Faivre; A Maurel; S Petrovski; ID Krantz; JM Tarpinian; JA Rosenfeld; BH Lee; DR Adams; ME Alejandro; P Allard; MS Azamian; CA Bacino; A Balasubramanyam; H Barseghyan; GF Batzli; AH Beggs; B Behnam; A Bican; DP Bick; CL Birch; D Bonner; BE Boone; BL Bostwick; LC Briere; DM Brown; M Brush; EA Burke; LC Burrage; S Chen; GD Clark; TR Coakley; JD Cogan; CM Cooper; H Cope; WJ Craigen; P D'Souza; M Davids; JG Dayal; EC Dell'Angelica; SU Dhar; A Dillon; KM Dipple; LA Donnell-Fink; N Dorrani; DC Dorset; ED Douine; DD Draper; DJ Eckstein; LT Emrick; CM Eng; A Eskin; C Esteves; T Estwick; C Ferreira; BL Fogel; ND Friedman; WA Gahl; E Glanton; RA Godfrey; DB Goldstein; SE Gould; JPF Gourdine; CA Groden

Journal article

Expanding the Spectrum of BAF-Related Disorders: De Novo Variants in SMARCC2 Cause a Syndrome with Intellectual Disability and Developmental Delay

K Machol, J Rousseau, S Ehresmann, T Garcia, TTM Nguyen, RC Spillmann, JA Sullivan, V Shashi, YH Jiang, N Stong, E Fiala, M Willing, R Pfundt, T Kleefstra, MT Cho, H McLaughlin, M Rosello Piera, C Orellana, F Martínez, A Caro-Llopis Show all

American Journal of Human Genetics | CELL PRESS | Published : 2019

DOI: 10.1016/j.ajhg.2018.11.007

Abstract

SMARCC2 (BAF170) is one of the invariable core subunits of the ATP-dependent chromatin remodeling BAF (BRG1-associated factor) complex and plays a crucial role in embryogenesis and corticogenesis. Pathogenic variants in genes encoding other components of the BAF complex have been associated with intellectual disability syndromes. Despite its significant biological role, variants in SMARCC2 have not been directly associated with human disease previously. Using whole-exome sequencing and a web-based gene-matching program, we identified 15 individuals with variable degrees of neurodevelopmental delay and growth retardation harboring one of 13 heterozygous variants in SMARCC2, most of them novel..

View full abstract

University of Melbourne Researchers

Slave Petrovski Author

Yaping Yang Author

Grants

Awarded by National Institutes of Health

Funding Acknowledgements

We thank the affected individuals and their families for their participation in this study. We thank Xinyu Cao from Duke for technical support for the mRNA expression analysis. We thank the CIHR and Fonds de recherche du Quebec - Sante (FRQS), Canada for clinician-scientist awards to P.M.C. Spanish individuals' study was supported by grant PI14/00350 (Instituto de Salud Carlos III - Accion Estrategica en Salud 2013-2016; FEDER -Fondo Europeo de Desarrollo Regional). Individual 10 was evaluated through the Duke Genome Sequencing Clinic, supported by the Duke University Health system, and partially funded by UCB Cell-tech. Partial research reported in this manuscript was supported by the NIH Common Fund, through the Office of Strategic Coordination/Office of the NIH Director under award numbers U01HG007672 (Duke University) and U01HG007942 (Baylor College of Medicine-Sequencing). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.