Genotype-Phenotype Correlation of Coffin-Siris Syndrome Caused by Mutations in SMARCB1, SMARCA4, SMARCE1, and ARID1A
Genotype-Phenotype Correlation of Coffin-Siris Syndrome Caused by Mutations in SMARCB1, SMARCA4, SMARCE1, and ARID1A
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DOI：
10.1002/ajmg.c.31407
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发表时间：
2014-09-01
影响因子：
3.1
通讯作者：
Okamoto, Nobuhiko
中科院分区：
文献类型：
--
作者：
Kosho, Tomoki;Okamoto, Nobuhiko
Coffin-Siris综合征（CSS）是一种罕见的先天性畸形综合征，最近发现是由BAF复合物的几个编码基因突变引起的。迄今为止，已有109例患者报告了突变：SMARCB 1（12%），SMARCA 4（11%），SMARCE 1（2%），ARID 1A（7%），ARID 1B（65%）和PHF 6（2%）。我们回顾了所有先前报道的SMARCB 1，SMARCA 4，SMARCE 1和ARID 1A突变患者的基因型-表型相关性，通过重新评估他们的临床和分子研究结果。CSS的主要特征包括不同程度的智力残疾（ID），主要影响言语、吸吮/进食困难、颅面（粗眉毛、长睫毛）、手指（第五手指或脚趾发育不良、第五指甲或脚趾甲发育不良）和其他特征（增生）。此外，SMARCB 1突变患者有严重的神经发育缺陷，包括严重的ID，癫痫发作，CNS结构异常，没有表达性词语以及脊柱侧凸。特别是，那些具有复发性突变p.Lys364del的人表现出惊人相似的表型，包括特征性的面部粗糙。SMARCA 4突变患者的颅面外观粗糙和行为异常较少。SMARCE 1突变患者具有从重度到中度ID的广泛表现。ARID 1A患者也具有从重度ID和可能导致早期死亡的浆液性内部并发症到轻度ID的广泛表现。SMARCB 1、SMARCA 4和SMARCE 1的突变预计会产生显性负效应或功能获得效应，而ARID 1A中的那些预期发挥功能丧失作用。(c)2014 Wiley Periodicals，Inc.
Coffin-Siris syndrome (CSS) is a rare congenital malformation syndrome, recently found to be caused by mutations in several genes encoding components of the BAF complex. To date, 109 patients have been reported with their mutations: SMARCB1 (12%), SMARCA4 (11%), SMARCE1 (2%), ARID1A (7%), ARID1B (65%), and PHF6 (2%). We review genotype-phenotype correlation of all previously reported patients with mutations in SMARCB1, SMARCA4, SMARCE1, and ARID1A through reassessment of their clinical and molecular findings. Cardinal features of CSS included variable degrees of intellectual disability (ID) predominantly affecting speech, sucking/feeding difficulty, and craniofacial (thick eyebrows, long eyelashes), digital (hypoplastic 5th fingers or toes, hypoplastic 5th fingernails or toenails), and other characteristics (hypertrichosis). In addition, patients with SMARCB1 mutations had severe neurodevelopmental deficits including severe ID, seizures, CNS structural abnormalities, and no expressive words as well as scoliosis. Especially, those with a recurrent mutation p.Lys364del represented strikingly similar phenotypes including characteristic facial coarseness. Patients with SMARCA4 mutations had less coarse craniofacial appearances and behavioral abnormalities. Patients with SMARCE1 mutations had a wide spectrum of manifestations from severe to moderate ID. Patients with ARID1A also had a wide spectrum of manifestations from severe ID and serous internal complications that could result in early death to mild ID. Mutations in SMARCB1, SMARCA4, and SMARCE1 are expected to exert dominant-negative or gain-of-function effects, whereas those in ARID1A are expected to exert loss-of-function effects. (c) 2014 Wiley Periodicals, Inc.