TY - JOUR
T1 - The variability of SMARCA4-related Coffin–Siris syndrome
T2 - Do nonsense candidate variants add to milder phenotypes?
AU - Li, Dong
AU - Ahrens-Nicklas, Rebecca C.
AU - Baker, Janice
AU - Bhambhani, Vikas
AU - Calhoun, Amy
AU - Cohen, Julie S.
AU - Deardorff, Matthew A.
AU - Fernández-Jaén, Alberto
AU - Kamien, Benjamin
AU - Jain, Mahim
AU - Mckenzie, Fiona
AU - Mintz, Mark
AU - Motter, Constance
AU - Niles, Kirsten
AU - Ritter, Alyssa
AU - Rogers, Curtis
AU - Roifman, Maian
AU - Townshend, Sharron
AU - Ward-Melver, Catherine
AU - Schrier Vergano, Samantha A.
N1 - Publisher Copyright:
© 2020 Wiley Periodicals LLC
PY - 2020/9/1
Y1 - 2020/9/1
N2 - 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.
AB - 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.
KW - BAF complex
KW - Coffin–Siris syndrome
KW - intellectual disability
KW - nonsense variants
KW - SMARCA4
UR - https://www.scopus.com/pages/publications/85088113265
U2 - 10.1002/ajmg.a.61732
DO - 10.1002/ajmg.a.61732
M3 - Article
C2 - 32686290
AN - SCOPUS:85088113265
SN - 1552-4825
VL - 182
SP - 2058
EP - 2067
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
IS - 9
ER -