Identification of Variants in SWI/SNF Complex Genes Associated with Neurodevelopmental Disorders

Chen Liang^1*Haihong Shi²Yanjuan Chen¹Xia Wang³Jieyuan Jin⁴Liqun Su¹Lijun Tang¹Huihong Li¹Fei Ling¹Haoxian Li¹Yanghui Zhang¹

• ¹Jiangmen Maternity and Child Health Care Hospital, Jiangmen, China
• ²Changzhou Maternal and Child Health Care Hospital, Changzhou, Jiangsu Province, China
• ³Xiangya Hospital, Central South University, Changsha, Hunan Province, China
• ⁴Shaoxing University, Shaoxing, Zhejiang Province, China

Neurodevelopmental disorder (NDDs) such as intellectual disability, developmental delay encompasses a diverse group of conditions caused by the disruptions in the central nervous system (CNS) during development. Variants in the SWItch/Sucrose non-fermentable (SWI/SNF) complex genes are significant contributors to NDDs. ARID2, ARID1B, and SMARCC2 are important subunits of the SWI/SNF complex, and their variants can also result in Coffin-Siris syndrome (CSS), a type of NDDs characterized by CNS disorders, global developmental delay, visual/hearing impairment, distinct facial features, and congenital heart disease (CHD). In this study, we recruited three children exhibiting NDD along with additional symptoms and identified three variants of SWI/SNF complex genes unreported in disease cohorts by whole-exome sequencing (WES) and Sanger sequencing, including a deletion variant of ARID2 (NM_152641: c.2901delC, p.Asn967LysfsX2), an insertion variant of ARID1B (NM_001374828: c.6532_6533insT, p.Trp2178LeufsX34), and a missense variant of SMARCC2 (NM_003075: c.2920C>G, p.Pro974Ala). Additionally, we compiled known variants in ARID2, ARID1B, and SMARCC2 associated with CSS/NDDs. Our identification broadened the variant spectrum of SWI/SNF genes and contributed to the genetic counseling and molecular diagnosis of NDDs.