Mingjie Liu1, Linlin Wan1, Chunrong Wang2, Hongyu Yuan1, Yun Peng1, Na Wan1, Zhichao Tang1, Xinrong Yuan1, Daji Chen1, Zhe Long3, Yuting Shi1,4, Rong Qiu5, Beisha Tang1,6,7,8,4, Hong Jiang1,9,6,7,8,4,10, Zhao Chen11,12,13,14. 1. Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China. 2. Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan, China. 3. Department of Neurology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China. 4. Hunan International Scientific and Technological Cooperation Base of Neurodegenerative and Neurogenetic Diseases, Changsha, China. 5. School of Computer Science and Engineering, Central South University, Changsha, Hunan, China. 6. Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, Hunan, China. 7. National Clinical Research Center for Geriatric Diseases, Central South University, Changsha, Hunan, China. 8. Laboratory of Medical Genetics, Central South University, Changsha, Hunan, China. 9. School of Basic Medical Science, Central South University, Changsha, Hunan, China. 10. National International Collaborative Research Center for Medical Metabolomics, Central South University, Changsha, Hunan, China. 11. Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China. czcf98@126.com. 12. Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, Hunan, China. czcf98@126.com. 13. National Clinical Research Center for Geriatric Diseases, Central South University, Changsha, Hunan, China. czcf98@126.com. 14. Hunan International Scientific and Technological Cooperation Base of Neurodegenerative and Neurogenetic Diseases, Changsha, China. czcf98@126.com.
Abstract
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.
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.
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