BICRA, a SWI/SNF Complex Member, Is Associated with BAF-Disorder Related Phenotypes in Humans and Model Organisms - Sorbonne Université Access content directly
Journal Articles American Journal of Human Genetics Year : 2020

BICRA, a SWI/SNF Complex Member, Is Associated with BAF-Disorder Related Phenotypes in Humans and Model Organisms

Scott Barish
Tahsin Stefan Barakat
  • Function : Author
Brittany Michel
  • Function : Author
Nazar Mashtalir
  • Function : Author
Jennifer Phillips
  • Function : Author
Alfredo Valencia
  • Function : Author
Berrak Ugur
  • Function : Author
Jeremy Wegner
  • Function : Author
Tiana Scott
  • Function : Author
Brett Bostwick
  • Function : Author
David Murdock
  • Function : Author
Hongzheng Dai
  • Function : Author
Elena Perenthaler
  • Function : Author
Anita Nikoncuk
  • Function : Author
Marjon van Slegtenhorst
  • Function : Author
Alice Brooks
  • Function : Author
Jessica Douglas
  • Function : Author
Lance Rodan
  • Function : Author
Catherine Nowak
  • Function : Author
Sian Ellard
  • Function : Author
Karen Stals
  • Function : Author
Sally Ann Lynch
  • Function : Author
Kendra Engleman
  • Function : Author
Dihong Zhou
  • Function : Author
Isabelle Thiffault
  • Function : Author
John Herriges
  • Function : Author
Jennifer Gass
  • Function : Author
Raymond Louie
  • Function : Author
Elliot Stolerman
  • Function : Author
Camerun Washington
  • Function : Author
Francesco Vetrini
  • Function : Author
Aiko Otsubo
  • Function : Author
Victoria Pratt
  • Function : Author
Erin Conboy
  • Function : Author
Kayla Treat
  • Function : Author
Nora Shannon
  • Function : Author
Jose Camacho
  • Function : Author
Emma Wakeling
  • Function : Author
Bo Yuan
  • Function : Author
Chun-An Chen
  • Function : Author
Jill Rosenfeld
  • Function : Author
Monte Westerfield
  • Function : Author
Michael Wangler
  • Function : Author
Shinya Yamamoto
  • Function : Author
Cigall Kadoch
  • Function : Author
Daryl Scott
  • Function : Author
Hugo Bellen

Abstract

SWI/SNF-related intellectual disability disorders (SSRIDDs) are rare neurodevelopmental disorders characterized by developmental disability, coarse facial features, and fifth digit/nail hypoplasia that are caused by pathogenic variants in genes that encode for members of the SWI/SNF (or BAF) family of chromatin remodeling complexes. We have identified 12 individuals with rare variants (10 loss-of-function, 2 missense) in the BICRA (BRD4 interacting chromatin remodeling complex-associated protein) gene, also known as GLTSCR1, which encodes a subunit of the non-canonical BAF (ncBAF) complex. These individuals exhibited neurodevelopmental phenotypes that include developmental delay, intellectual disability, autism spectrum disorder, and behavioral abnormalities as well as dysmorphic features. Notably, the majority of individuals lack the fifth digit/nail hypoplasia phenotype, a hallmark of most SSRIDDs. To confirm the role of BICRA in the development of these phenotypes, we performed functional characterization of the zebrafish and Drosophila orthologs of BICRA. In zebrafish, a mutation of bicra that mimics one of the loss-of-function variants leads to craniofacial defects possibly akin to the dysmorphic facial features seen in individuals harboring putatively pathogenic BICRA variants. We further show that Bicra physically binds to other non-canonical ncBAF complex members, including the BRD9/7 ortholog, CG7154, and is the defining member of the ncBAF complex in flies. Like other SWI/SNF complex members, loss of Bicra function in flies acts as a dominant enhancer of position effect variegation but in a more context-specific manner. We conclude that haploinsufficiency of BICRA leads to a unique SSRIDD in humans whose phenotypes overlap with those previously reported.

Dates and versions

hal-04566230 , version 1 (02-05-2024)

Identifiers

Cite

Scott Barish, Tahsin Stefan Barakat, Brittany Michel, Nazar Mashtalir, Jennifer Phillips, et al.. BICRA, a SWI/SNF Complex Member, Is Associated with BAF-Disorder Related Phenotypes in Humans and Model Organisms. American Journal of Human Genetics, 2020, 107 (6), pp.1096-1112. ⟨10.1016/j.ajhg.2020.11.003⟩. ⟨hal-04566230⟩
0 View
0 Download

Altmetric

Share

Gmail Facebook X LinkedIn More