Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Am J Med Genet A. 2020 Sep;182(9):2058-2067. doi: 10.1002/ajmg.a.61732. Epub 2020 Jul 20.
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.
SMARCA4 在人类中编码 BRG1-/BRM 相关因子(BAF)或多溴相关 BAF(PBAF)复合物的核心 ATP 酶亚基,部分负责染色质重塑和转录调控。该基因和其他编码 BAF/PBAF 复合物的基因中的变异与 Coffin-Siris 综合征有关,这是一种多种先天异常综合征,其特征为学习和发育差异、粗糙的面部特征、多毛症以及手和脚的第五个数字/指甲发育不良。先前已经报道了具有 SMARCA4 变异的个体,并且似乎表现出可变的表型。我们在此描述了 Coffin-Siris 综合征/BAF 通路疾病登记处的 15 名无关个体的 SMARCA4 变异队列,他们进一步表现出学习障碍和健康问题严重程度和程度的可变性。在该队列中,我们还报告了两名具有新无义变异的个体,他们似乎表现出较轻的学习/行为差异表型,并且没有器官系统受累。
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