title: Mutations in ARID2 are associated with intellectual disabilities.
abstract: The etiology of intellectual disabilities (ID) remains unknown for the majority of patients. Due to reduced reproductive fitness in many individuals with ID, de novo mutations account for a significant portion of severe ID. The ATP-dependent SWI/SNF chromatin modifier has been linked with neurodevelopmental disorders including ID and autism. ARID2 is an intrinsic component of polybromo-associated BAF (PBAF), the SWI/SNF subcomplex. In this study, we used clinical whole exome sequencing (WES) in proband-parent-trios to identify the etiology of ID. We identified four independent, novel, loss of function variants in ARID2 gene in four patients, three of which were confirmed to be de novo. The patients all have ID and share other clinical characteristics including attention deficit hyperactivity disorder, short stature, dysmorphic facial features, and Wormian bones. All four novel variants are predicted to lead to a premature termination with the loss of the two conservative zinc finger motifs. This is the first report of mutations in ARID2 associated with developmental delay and ID.
authors.affiliation: Department of Pediatrics, Columbia University Medical Center, 1150 St. Nicholas Avenue, New York, NY, 10032, USA.
authors.forename: Linshan
authors.initials: L
authors.lastname: Shang
authors.affiliation: GeneDx, Gaithersburg, MD, USA.
authors.forename: Megan T
authors.initials: MT
authors.lastname: Cho
authors.affiliation: GeneDx, Gaithersburg, MD, USA.
authors.forename: Kyle
authors.initials: K
authors.lastname: Retterer
authors.affiliation: GeneDx, Gaithersburg, MD, USA.
authors.forename: Leandra
authors.initials: L
authors.lastname: Folk
authors.affiliation: Department of Pediatrics, Division of Genetics and Metabolism, University of Virginia, Charlottesville, VA, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Humberson
authors.affiliation: Department of Pediatrics, Division of Genetics, San Antonio Military Medical Center, San Antonio, TX, USA.
authors.forename: Luis
authors.initials: L
authors.lastname: Rohena
authors.affiliation: Department of Pediatrics and Human Development, Michigan State University, East Lansing, MI, USA.
authors.forename: Alpa
authors.initials: A
authors.lastname: Sidhu
authors.affiliation: Department of Pediatrics and Human Development, Michigan State University, East Lansing, MI, USA.
authors.forename: Sheila
authors.initials: S
authors.lastname: Saliganan
authors.affiliation: Department of Pediatrics, Columbia University Medical Center, 1150 St. Nicholas Avenue, New York, NY, 10032, USA.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Iglesias
authors.affiliation: GeneDx, Gaithersburg, MD, USA.
authors.forename: Patrik
authors.initials: P
authors.lastname: Vitazka
authors.affiliation: GeneDx, Gaithersburg, MD, USA.
authors.forename: Jane
authors.initials: J
authors.lastname: Juusola
authors.affiliation: Analytical and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.|Broad Institute of MIT and Harvard, Cambridge, MA, USA.|Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA.
authors.forename: Anne H
authors.initials: AH
authors.lastname: O'Donnell-Luria
authors.affiliation: Department of System Biology and Biomedical Informatics, Columbia University Medical Center, New York, NY, 10032, USA.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Department of Pediatrics, Columbia University Medical Center, 1150 St. Nicholas Avenue, New York, NY, 10032, USA. wkc15@columbia.edu.|Department of Medicine, Columbia University Medical Center, New York, NY, USA. wkc15@columbia.edu.
authors.forename: Wendy K
authors.initials: WK
authors.lastname: Chung
mesh_terms: D000293:Adolescent; D002648:Child; D002658:Developmental Disabilities / Q000235:genetics*; D059472:Exome; D005260:Female; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D009154:Mutation; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C512511:ARID2 protein, human; D014157:Transcription Factors
keywords: ARID2; De novo mutations; Intellectual disabilities; SWI/SNF chromatin modifier; Whole exome sequencing