Abstract：
Coffin-Siris syndrome (CSS) (OMIM #135900) involves multiple congenital malformations, including hypotonia, short stature, sparse scalp hair, a coarse face, prominent eyebrows, a wide mouth, delayed bone age, and hypoplastic or absent fifth fingers/toes or nails, together with developmental delay. The cause of CSS is suggested to be related to alterations in the BRG- or HRBM-associated factor (BAF) pathway in humans. In this gene family, pathogenic variations in the AT-rich interactive domain-containing protein 1B (ARID1B) gene are revealed to be a significant element causing neurodevelopmental disability in patients with CSS. Herein, we describe the clinical features and gene variations in four Chinese patients with CSS. All the patients shared common features of short fifth fingers/toes or hypoplastic nails, coarse facial features, thick eyebrows, long cilia, a flat nasal bridge, a broad nose, a wide mouth, a high palate, and hypotonia. Besides, they had an intellectual disability, language, and motor developmental delay. Candidate genes were screened for variations using polymerase chain reaction (PCR) and sequencing. The variations were sequenced by next-generation sequencing and confirmed by first-generation sequencing. Exome sequencing suggested four de novo variations in the ARID1B gene in four unrelated patients. These included two frameshift variations (c.3581delC, c.6661_6662insG) and two nonsense variations (c.1936C>T, c.2248C>T). Of the four variations, three variations were novel. The results in our present study broaden the understanding of the disease and further interpret the molecular genetic mechanism of these rare variations in CSS.
摘要：
Coffin-Siris综合征（CSS）（OMIM#135900）涉及多种先天性畸形，包括低张力,身材矮小,稀疏的头皮头发，粗糙的脸，突出的眉毛,大嘴巴,骨龄延迟，第五手指/脚趾或指甲发育不良或缺失，以及发育迟缓。CSS的原因被认为与人类BBG或HRBM相关因子（BAF）途径的改变有关。在这个基因家族中，富含AT的含相互作用域的蛋白1B（ARID1B）基因的致病变异被发现是导致CSS患者神经发育障碍的重要因素。在这里，我们描述了四名中国CSS患者的临床特征和基因变异。所有患者都有第五指/脚趾短或指甲发育不良的共同特征，粗糙的面部特征，浓眉,长纤毛,扁平的鼻梁,宽阔的鼻子，大嘴巴,高上颚，和低张力。此外,他们有智力障碍，语言,和运动发育迟缓。使用聚合酶链反应(PCR)和测序筛选候选基因的变异。通过下一代测序对变异进行测序，并通过第一代测序进行确认。外显子组测序表明，在四名无关患者中，ARID1B基因有四个从头变异。其中包括两个移码变体（c.3581delC，c.6661_6662insG)和两个无意义变化(c.1936C>T，c.2248C>T）。在四种变化中，三个变化是新颖的。我们本研究的结果拓宽了对该疾病的理解，并进一步解释了CSS中这些罕见变异的分子遗传机制。
