1. The variability of SMARCA4-related Coffin-Siris syndrome: Do nonsense candidate variants add to milder phenotypes?
- Author
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Janice Baker, Curtis Rogers, Mark Mintz, Maian Roifman, Vikas Bhambhani, Fiona Haslam McKenzie, Julie S. Cohen, Constance Motter, Amy Calhoun, Benjamin Kamien, Alyssa Ritter, Catherine Ward-Melver, Dong Li, Rebecca C. Ahrens-Nicklas, Sharron Townshend, Matthew A. Deardorff, Kirsten M. Niles, Samantha A. Schrier Vergano, Alberto Fernández-Jaén, and Mahim Jain
- Subjects
Hypertrichosis ,Male ,Adolescent ,Chromosomal Proteins, Non-Histone ,media_common.quotation_subject ,Nonsense ,Micrognathism ,Biology ,Genética humana ,Chromatin remodeling ,Intellectual Disability ,Genetics ,medicine ,Humans ,Abnormalities, Multiple ,Genetic Predisposition to Disease ,Síndrome de Coffin-lowry ,Child ,Gene ,Coffin–Siris syndrome ,Ciencias médicas ,Genetics (clinical) ,Genetic Association Studies ,media_common ,Coarse facial features ,DNA Helicases ,Infant ,Nuclear Proteins ,medicine.disease ,Phenotype ,DNA-Binding Proteins ,Codon, Nonsense ,Child, Preschool ,Face ,SMARCA4 ,Female ,Hand Deformities, Congenital ,Neck ,Transcription Factors - Abstract
SMARCA4 encodes a central ATPase subunit in the BRG1-/BRM-associated factors (BAF) or polybromo-associated BAF (PBAF) complex in humans, which is responsible in part for chromatin remodeling and transcriptional regulation. Variants in this and other genes encoding BAF/PBAF complexes have been implicated in Coffin–Siris Syndrome, a multiple congenital anomaly syndrome classically characterized by learning and developmental differences, coarse facial features, hypertrichosis, and underdevelopment of the fifth digits/nails of the hands and feet. Individuals with SMARCA4 variants have been previously reported and appear to display a variable phenotype. We describe here a cohort of 15 unrelated individuals with SMARCA4 variants from the Coffin–Siris syndrome/BAF pathway disorders registry who further display variability in severity and degrees of learning impairment and health issues. Within this cohort, we also report two individuals with novel nonsense variants who appear to have a phenotype of milder learning/behavioral differences and no organ-system involvement. Sin financiación 2.802 JCR (2020) Q3, 104/176 Genetics & Heredity 1.064 SJR (2020) Q2, 127/340 Genetics No data IDR 2020 UEM
- Published
- 2020