Phenotypic and Molecular Spectrum of Patients With Switch/sucrose Nonfermenting Complex-related Intellectual Disabilities in Korea

Background: The switch/sucrose nonfermenting (SWI/SNF) complex is an adenosine triphosphate (ATP)-dependent chromatin-remodeling complex associated with the regulation of DNA accessibility. Germline mutations in the components of the SWI/SNF complex are related to human developmental disorder, including the Coffin–Siris syndrome (CSS), Nicolaides–Baraitser syndrome (NCBRS), and nonsyndromic intellectual disability. These disorders are collectively referred to as SWI/SNF-related intellectual disability (SSRIDD). Methods: : Whole exome sequencing was performed in 564 Korean patients with neurodevelopmental disorders. Twelve patients with SSRIDDs (2.1%) were included, and their medical records were retrospectively analyzed. Results: : ARID1B , found in eight patients, were the most frequently-altered gene. Four patients harbored mutations in SMARCA4 , SMARCB1 , ARID2 , and SMARCA2. Ten patients were diagnosed with CSS, and one patient without typical phenotypes was classified as ARID1B -related intellectual disability. Another patient harboring the SMARCA2 mutation was diagnosed with NCBRS. All pathogenic variants in ARID1B were truncating, whereas variants in SMARCA2 , SMARCB1 , and SMARCA4 were nontruncating (missense) mutations. Frequently-observed phenotypes were thick eyebrows (10/12), hypertrichosis (8/12), coarse face (8/12), thick lips (8/12), and long eyelashes (8/12). Developmental delay was observed in all patients, and profound speech delay was also characteristic. Agenesis or hypoplasia of the corpus callosum was found in half of the patients (6/12). Conclusions: : SSRIDD holds a broad disease spectrum, including NCBRS, CSS, and ARID1B -related intellectual disability. Thus, the SSRIDD should be considered as a small but important cause of human developmental disorder.