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ARID2,一种导致 Coffin-Siris 综合征的较温和原因?通过 17 个额外个体拓宽表型。

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

机构信息

Division of Medical Genetics and Metabolism, Children's Hospital of The King's Daughters, Norfolk, Virginia, USA.

Department of Pediatrics, Eastern Virginia Medical School, Norfolk, Virginia, USA.

出版信息

Am J Med Genet A. 2024 Jun;194(6):e63540. doi: 10.1002/ajmg.a.63540. Epub 2024 Jan 19.


DOI:10.1002/ajmg.a.63540
PMID:38243407
Abstract

Coffin-Siris Syndrome (CSS, MIM 135900) is now a well-described genetic condition caused by pathogenic variants in the Bromocriptine activating factor (BAF) complex, including ARID1B, ARID1A, ARID2, SMARCA4, SMARCE1, SMARCB1, SOX11, SMARCC2, DPF2, and more recently, BICRA. Individuals with CSS have a spectrum of various medical challenges, most often evident at birth, including feeding difficulties, hypotonia, organ-system anomalies, and learning and developmental differences. The classic finding of fifth digit hypo- or aplasia is seen variably. ARID2, previously described, is one of the less frequently observed gene changes in CSS. Although individuals with ARID2 have been reported to have classic features of CSS including hypertrichosis, coarse facial features, short stature, and fifth digit anomalies, as with many of the other CSS genes, there appears to be a spectrum of phenotypes. We report here a cohort of 17 individuals with ARID2 variants from the Coffin-Siris/BAF clinical registry and detail their medical challenges as well as developmental progress. Feeding difficulties, hypotonia, and short stature occur often, and hip dysplasia appears to occur more often than with other genes, however more severe medical challenges such as significant brain and cardiac malformations are rarer. Individuals appear to have mild to moderate intellectual impairment and may carry additional diagnoses such as ADHD. Further phenotypic description of this gene will aid clinicians caring for individuals with this rarer form of CSS.

摘要

Coffin-Siris 综合征(CSS,MIM 135900)是一种已被充分描述的遗传疾病,由 Bromocriptine 激活因子(BAF)复合物的致病性变异引起,包括 ARID1B、ARID1A、ARID2、SMARCA4、SMARCE1、SMARCB1、SOX11、SMARCC2、DPF2 等,最近还包括 BICRA。CSS 患者存在各种医疗挑战,大多数在出生时就很明显,包括喂养困难、低张力、器官系统异常以及学习和发育差异。第五指发育不全或缺失是 CSS 的经典表现之一,但表现形式存在差异。先前描述过的 ARID2 是 CSS 中较少观察到的基因变化之一。尽管携带 ARID2 变异的个体表现出 CSS 的经典特征,包括多毛症、粗糙面容、身材矮小和第五指异常,但与许多其他 CSS 基因一样,其表型似乎存在一定的范围。我们在此报告了来自 Coffin-Siris/BAF 临床登记处的 17 名携带 ARID2 变异的个体,并详细描述了他们的医疗挑战和发育进展。喂养困难、低张力和身材矮小经常发生,髋关节发育不良似乎比其他基因更常见,但更严重的医疗挑战如严重的大脑和心脏畸形则较为罕见。个体似乎存在轻度至中度智力障碍,可能还伴有其他诊断,如注意力缺陷多动障碍。进一步描述该基因的表型将有助于照顾这种罕见 CSS 形式的患者的临床医生。

相似文献

[1]
ARID2, a milder cause of Coffin-Siris Syndrome? Broadening the phenotype with 17 additional individuals.

Am J Med Genet A. 2024-6

[2]
SMARCE1, a rare cause of Coffin-Siris Syndrome: Clinical description of three additional cases.

Am J Med Genet A. 2016-8

[3]
Genotype-Phenotype Correlations in 208 Individuals with Coffin-Siris Syndrome.

Genes (Basel). 2021-6-19

[4]
First data from a parent-reported registry of 81 individuals with Coffin-Siris syndrome: Natural history and management recommendations.

Am J Med Genet A. 2018-10-1

[5]
The variability of SMARCA4-related Coffin-Siris syndrome: Do nonsense candidate variants add to milder phenotypes?

Am J Med Genet A. 2020-9

[6]
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

[7]
Coffin-Siris syndrome and the BAF complex: genotype-phenotype study in 63 patients.

Hum Mutat. 2013-8-30

[8]
Heterozygosity for ARID2 loss-of-function mutations in individuals with a Coffin-Siris syndrome-like phenotype.

Hum Genet. 2017-3

[9]
Genotype and phenotype in 18 Chinese patients with Coffin-Siris syndrome.

Am J Med Genet A. 2021-7

[10]
Coffin-Siris syndrome is a SWI/SNF complex disorder.

Clin Genet. 2014-6

引用本文的文献

[1]
Identification of variants in SWI/SNF complex genes associated with neurodevelopmental disorders.

Front Genet. 2025-7-8

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