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SMARCA4 相关 Coffin-Siris 综合征的变异性:无义候选变异是否会导致更轻微的表型?

The variability of SMARCA4-related Coffin-Siris syndrome: Do nonsense candidate variants add to milder phenotypes?

机构信息

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.

出版信息

Am J Med Genet A. 2020 Sep;182(9):2058-2067. doi: 10.1002/ajmg.a.61732. Epub 2020 Jul 20.


DOI:10.1002/ajmg.a.61732
PMID:32686290
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.

摘要

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。

相似文献

[1]
The variability of SMARCA4-related Coffin-Siris syndrome: Do nonsense candidate variants add to milder phenotypes?

Am J Med Genet A. 2020-9

[2]
Coffin-Siris syndrome is a SWI/SNF complex disorder.

Clin Genet. 2014-6

[3]
Genotype-phenotype correlation of Coffin-Siris syndrome caused by mutations in SMARCB1, SMARCA4, SMARCE1, and ARID1A.

Am J Med Genet C Semin Med Genet. 2014-9

[4]
Numerous BAF complex genes are mutated in Coffin-Siris syndrome.

Am J Med Genet C Semin Med Genet. 2014-9

[5]
SMARCA4 inactivating mutations cause concomitant Coffin-Siris syndrome, microphthalmia and small-cell carcinoma of the ovary hypercalcaemic type.

J Pathol. 2017-9

[6]
ARID2, a milder cause of Coffin-Siris Syndrome? Broadening the phenotype with 17 additional individuals.

Am J Med Genet A. 2024-6

[7]
Genotype-Phenotype Correlations in 208 Individuals with Coffin-Siris Syndrome.

Genes (Basel). 2021-6-19

[8]
A case of Coffin-Siris syndrome with severe congenital heart disease and a novel variant.

Cold Spring Harb Mol Case Stud. 2019-6-3

[9]
SMARCE1, a rare cause of Coffin-Siris Syndrome: Clinical description of three additional cases.

Am J Med Genet A. 2016-8

[10]
Coffin-Siris syndrome and the BAF complex: genotype-phenotype study in 63 patients.

Hum Mutat. 2013-8-30

引用本文的文献

[1]
-related Coffin-Siris syndrome in newborn: a case report and literature review.

Front Pediatr. 2025-1-21

[2]
BRG1 programs PRC2-complex repression and controls oligodendrocyte differentiation and remyelination.

J Cell Biol. 2024-7-1

[3]
Spliceosome malfunction causes neurodevelopmental disorders with overlapping features.

J Clin Invest. 2024-1-2

[4]
mutation causes human otosclerosis and a similar phenotype in mice.

J Med Genet. 2024-1-19

[5]
Role of brahma-related gene 1/brahma-associated factor subunits in neural stem/progenitor cells and related neural developmental disorders.

World J Stem Cells. 2023-4-26

[6]
Pitfalls of whole exome sequencing in undefined clinical conditions with a suspected genetic etiology.

Genes Genomics. 2023-5

[7]
Identifying phenotypic expansions for congenital diaphragmatic hernia plus (CDH+) using DECIPHER data.

Am J Med Genet A. 2022-10

[8]
Discovering a new part of the phenotypic spectrum of Coffin-Siris syndrome in a fetal cohort.

Genet Med. 2022-8

[9]
Rare Hereditary Gynecological Cancer Syndromes.

Int J Mol Sci. 2022-1-29

[10]
Novel diagnostic DNA methylation episignatures expand and refine the epigenetic landscapes of Mendelian disorders.

HGG Adv. 2021-12-3

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