Abstract：
Coffin-Siris syndrome (CSS) is a rare congenital syndrome characterized by developmental delay, intellectual disability, microcephaly, coarse face and hypoplastic nail of the fifth digits. Heterozygous variants of different BAF complex-related genes were reported to cause CSS, including ARID1A and SMARCA4. So far, no CSS patients with ARID1A and SMARCA4 variants have been reported in China.
The aim of the current study was to identify the causes of two Chinese patients with congenital growth deficiency and intellectual disability.
Genomic DNA was extracted from the peripheral venous blood of patients and their family members. Genetic analysis included whole-exome and Sanger sequencing. Pathogenicity assessments of variants were performed according to the guideline of the American College of Medical Genetics and Genomics. The phenotypic characteristics of all CSS subtypes were summarized through literature review.
We identified two Chinese CSS patients carrying novel variants of ARID1A and SMARCA4 respectively. The cases presented most core symptoms of CSS except for the digits involvement. Additionally, we performed a review of the phenotypic characteristics in CSS, highlighting phenotypic varieties and related potential causes.
We reported the first Chinese CSS2 and CSS4 patients with novel variants of ARID1A and SMARCA4. Our study expanded the genetic and phenotypic spectrum of CSS, providing a comprehensive overview of genotype-phenotype correlations of CSS.
The aim of the current study was to identify the causes of two Chinese patients with congenital growth deficiency and intellectual disability.
Genomic DNA was extracted from the peripheral venous blood of patients and their family members. Genetic analysis included whole-exome and Sanger sequencing. Pathogenicity assessments of variants were performed according to the guideline of the American College of Medical Genetics and Genomics. The phenotypic characteristics of all CSS subtypes were summarized through literature review.
We identified two Chinese CSS patients carrying novel variants of ARID1A and SMARCA4 respectively. The cases presented most core symptoms of CSS except for the digits involvement. Additionally, we performed a review of the phenotypic characteristics in CSS, highlighting phenotypic varieties and related potential causes.
We reported the first Chinese CSS2 and CSS4 patients with novel variants of ARID1A and SMARCA4. Our study expanded the genetic and phenotypic spectrum of CSS, providing a comprehensive overview of genotype-phenotype correlations of CSS.
摘要：
Coffin-Siris综合征（CSS）是一种罕见的先天性综合征，以发育迟缓为特征，智力残疾,小头畸形,粗糙的脸和五位数的发育不良的指甲。据报道，不同BAF复合物相关基因的杂合变体会导致CSS，包括ARID1A和SMARCA4。到目前为止,在中国没有报道有ARID1A和SMARCA4变异的CSS患者。
本研究的目的是确定两名患有先天性生长缺陷和智力残疾的中国患者的原因。
从患者及其家庭成员的外周静脉血中提取基因组DNA。遗传分析包括全外显子组和Sanger测序。根据美国医学遗传学和基因组学学院的指南进行变体的致病性评估。通过文献综述总结了所有CSS亚型的表型特征。
我们确定了两名分别携带ARID1A和SMARCA4新变种的中国CSS患者。除了数字受累外，这些病例表现出CSS的大多数核心症状。此外,我们对CSS中的表型特征进行了回顾，突出表型品种和相关潜在原因。
我们报道了首例出现新型ARID1A和SMARCA4变异的中国CSS2和CSS4患者。我们的研究扩展了CSS的遗传和表型谱，全面概述了CSS的基因型-表型相关性。
本研究的目的是确定两名患有先天性生长缺陷和智力残疾的中国患者的原因。
从患者及其家庭成员的外周静脉血中提取基因组DNA。遗传分析包括全外显子组和Sanger测序。根据美国医学遗传学和基因组学学院的指南进行变体的致病性评估。通过文献综述总结了所有CSS亚型的表型特征。
我们确定了两名分别携带ARID1A和SMARCA4新变种的中国CSS患者。除了数字受累外，这些病例表现出CSS的大多数核心症状。此外,我们对CSS中的表型特征进行了回顾，突出表型品种和相关潜在原因。
我们报道了首例出现新型ARID1A和SMARCA4变异的中国CSS2和CSS4患者。我们的研究扩展了CSS的遗传和表型谱，全面概述了CSS的基因型-表型相关性。
