Cheng Shirley S W, Luk Ho-Ming, Mok Myth Tsz-Shun, Leung Sha-Sha, Lo Ivan F M
Clinical Genetic Service, Department of Health, HKSAR, Hong Kong, China.
Am J Med Genet A. 2021 Jul;185(7):2250-2261. doi: 10.1002/ajmg.a.62187. Epub 2021 Mar 26.
Coffin-Siris syndrome (CSS, MIM# 1359200) is a multisystem congenital disorder characterized by coarse facial features, hypoplasia of the fifth digits and nails, and intellectual disability. It is a genetically heterogeneous condition caused by pathogenic variants in genes encoding proteins of the BAF (BRG1-associated factors) chromatin modeling complex and its downstream transcriptional factor. To date over 220 CSS individuals with pathogenic variants found have been described in the literature. This case series reported 18 molecularly confirmed Chinese individuals (17 with ARIDIB (OMIM614556) variants and one with SMARCB1 (OMIM601607) variant) from 17 unrelated families in Hong Kong. The clinical features of these 18 Chinese CSS patients together with two previously reported Chinese patients with ARID1B variants were reviewed. Among the 19 Chinese patients with ARID1B variants, our data suggested a lower prevalence of feeding problem, autistic features, agenesis of corpus callosum (ACC) or partial/hypoplasia of corpus callosum, and sparse hair when compared with previous reports. There was appearing higher prevalence of digital hypoplasia. Digital hypoplasia was observed to become less noticeable with time in some patients. This report highlighted the age-dependent phenotypic presentation of CSS and ethnicity-related effect on ARID1B-CSS phenotype. Moreover, this series included the first family with molecularly confirmed maternal somatic mosaicism of ARID1B variant leading to familial CSS recurrence.
科芬-西里斯综合征（CSS，MIM# 1359200）是一种多系统先天性疾病，其特征为面部特征粗糙、第五指及指甲发育不全以及智力残疾。它是一种基因异质性疾病，由编码BAF（BRG1相关因子）染色质建模复合体及其下游转录因子的基因中的致病变异引起。迄今为止，文献中已描述了超过220例发现有致病变异的CSS患者。本病例系列报告了来自香港17个无关家庭的18例经分子确诊的中国患者（17例携带ARIDIB（OMIM614556）变异，1例携带SMARCB1（OMIM601607）变异）。对这18例中国CSS患者以及之前报道的2例携带ARID1B变异的中国患者的临床特征进行了回顾。在19例携带ARID1B变异的中国患者中，我们的数据表明，与之前的报道相比，喂养问题、自闭症特征、胼胝体发育不全（ACC）或胼胝体部分发育不全/发育不全以及头发稀疏的患病率较低。指发育不全的患病率似乎较高。在一些患者中，随着时间的推移，指发育不全变得不那么明显。本报告强调了CSS的年龄依赖性表型表现以及种族对ARID1B-CSS表型的影响。此外，该系列包括首个经分子确诊的携带ARID1B变异的母体体细胞镶嵌导致家族性CSS复发的家庭。
