Tan Yuxia, Chen Jun, Li Yutang, Liu Yedan, Wang Yu, Xia Shungang, Chen Liping, Wei Wei, Chen Zongbo
Department of Pediatrics, The Affiliated Hospital of Qingdao University, Haier Road; Department of Pediatrics, Zibo City Maternal and Child Health Hospital, Zibo City, Shandong Province, Qingdao, Shandong, 266034, China.
Department of Neurology and Rehabilitation, Qingdao Women and Children's Hospital, Qingdao University. No. 6 Tongfu Road, Qingdao, Shandong, 266034, China.
Neurol India. 2022 Sep-Oct;70(5):2174-2179. doi: 10.4103/0028-3886.359283.
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.
科芬-西里斯综合征（CSS）（OMIM #135900）涉及多种先天性畸形，包括肌张力减退、身材矮小、头皮毛发稀疏、面容粗糙、眉毛浓密、嘴巴宽大、骨龄延迟以及第五指/趾或指甲发育不全或缺失，同时伴有发育迟缓。CSS的病因被认为与人类BRG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的相互作用结构域蛋白1B（ARID1B）基因的致病性变异被发现是导致CSS患者神经发育障碍的一个重要因素。在此，我们描述了4例中国CSS患者的临床特征和基因变异。所有患者都有第五指/趾短小或指甲发育不全、面部特征粗糙、眉毛浓密、睫毛长、鼻梁扁平、鼻子宽阔、嘴巴宽大、上颚高拱以及肌张力减退等共同特征。此外，他们还存在智力残疾、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4例无关患者的ARID1B基因存在4种新生变异。其中包括2种移码变异（c.3581delC，c.6661_6662insG）和2种无义变异（c.1936C>T，c.2248C>T）。在这4种变异中，有3种变异是新发现的。我们目前的研究结果拓宽了对该疾病的认识，并进一步解释了CSS中这些罕见变异的分子遗传机制。
