Coffin-Siris syndrome in two chinese patients with novel pathogenic variants of ARID1A and SMARCA4

• Published in: Genes & genomics Vol. 44; no. 9; pp. 1061 - 1070
• Main Authors: Liu, Mingjie, Wan, Linlin, Wang, Chunrong, Yuan, Hongyu, Peng, Yun, Wan, Na, Tang, Zhichao, Yuan, Xinrong, Chen, Daji, Long, Zhe, Shi, Yuting, Qiu, Rong, Tang, Beisha, Jiang, Hong, Chen, Zhao
• Format: Journal Article
• Language: English
• Published: Singapore Springer Nature Singapore 01.09.2022; Springer; Springer Nature B.V; 한국유전학회
• Subjects: Analysis; Animal Genetics and Genomics; Biomedical and Life Sciences; Coffin-Siris syndrome; DNA sequencing; Genetic analysis; Genetic disorders; Genomics; Genotypes; Human Genetics; Intellectual disabilities; Life Sciences; Literature reviews; Medical genetics; Microbial Genetics and Genomics; Microcephaly; Nucleotide sequencing; Pathogenicity; Patients; Phenotypes; Plant Genetics and Genomics; Research Article; 생물학; Novel variants; Clinical heterogeneity; Coffin-Siris syndrome; ARID1A; SMARCA4
• DOI: 10.1007/s13258-022-01231-2
• ISSN: 1976-9571

Background 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. Objective The aim of the current study was to identify the causes of two Chinese patients with congenital growth deficiency and intellectual disability. Methods 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. Results 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. Conclusions 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.