title: A novel familial autosomal dominant mutation in ARID1B causing neurodevelopmental delays, short stature, and dysmorphic features.
abstract: Recent studies have identified mutations in the ARID1B gene responsible for neurodevelopmental delays, intellectual disability, growth delay, and dysmorphic features. ARID1B encodes a subunit of the BAF chromatin-remodeling complex, and mutations in multiple components of the BAF complex have been implicated as causes of Coffin-Siris syndrome, Nicolaides-Baraitser syndrome, and non-syndromic intellectual disability. The majority of documented pathogenic ARID1B mutations to date have arisen in a sporadic, de novo manner with no reports of inheritance of a pathogenic mutation from an affected parent. We describe here two patients (a 21-year-old female and her 21-month-old son) with a novel frameshift mutation in ARID1B inherited in an autosomal dominant fashion in the affected offspring. Both patients presented with neurodevelopmental delays, growth delay, and dysmorphic features including prominent nose with full nasal tip, long philtrum, and high-arched palate. Exome sequencing analysis in the female patient demonstrated a heterozygous deletion of nucleotide 1259 of the ARID1B gene (c.1259delA) resulting in a frameshift and creation of a premature stop codon. Further family testing by targeted Sanger sequencing confirmed that this arose as a de novo mutation in the mother and was passed on to her affected son. The clinical features of both patients are felt to be consistent with an ARID1B-related disorder. To our knowledge, this is the first report of a pathogenic mutation in ARID1B being passed from an affected parent to their offspring. © 2016 Wiley Periodicals, Inc.
authors: Department of Neurology, College of Medicine, Medical University of South Carolina, Charleston, South Carolina.
authors: Joshua A
authors: JA
authors: Smith
authors: Department of Neurology, College of Medicine, Medical University of South Carolina, Charleston, South Carolina.|Department of Pediatrics, College of Medicine, Medical University of South Carolina, Charleston, South Carolina.|Clinical Genetics, Greenwood Genetic Center, Greenwood, South Carolina.
authors: Kenton R
authors: KR
authors: Holden
authors: Clinical Genetics, Greenwood Genetic Center, Greenwood, South Carolina.
authors: Michael J
authors: MJ
authors: Friez
authors: Clinical Genetics, Greenwood Genetic Center, Greenwood, South Carolina.
authors: Julie R
authors: JR
authors: Jones
authors: Clinical Genetics, Greenwood Genetic Center, Greenwood, South Carolina.
authors: Michael J
authors: MJ
authors: Lyons
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics*; D000483:Alleles; D019943:Amino Acid Substitution; D004268:DNA-Binding Proteins / Q000235:genetics*; D002658:Developmental Disabilities / Q000175:diagnosis / Q000235:genetics*; D004392:Dwarfism / Q000175:diagnosis / Q000235:genetics*; D059472:Exome; D019066:Facies; D005260:Female; D005799:Genes, Dominant; D056726:Genetic Association Studies; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D010641:Phenotype; D014157:Transcription Factors / Q000235:genetics*; D055815:Young Adult
chemical_list: C497837:ARID1B protein, human; D004268:DNA-Binding Proteins; D014157:Transcription Factors
keywords: ARID1B; autosomal dominant inheritance; dysmorphic features; exome sequencing; intellectual disability