# Clinical and Genetic Analysis of SMARCC2‐Related Diseases in Three Chinese Patients

## TL;DR

This study reports on three Chinese patients with SMARCC2 gene variants, expanding the understanding of the genetic and clinical features of SMARCC2-related diseases.

## Contribution

The study identifies new SMARCC2 variants and broadens the clinical description of SMARCC2-related disorders.

## Key findings

- Three patients with SMARCC2 variants showed mild to moderate developmental delay and other neurological symptoms.
- New de novo variants in SMARCC2 were identified, contributing to the genetic spectrum of the disorder.
- Clinical features suggest a need for redefining SMARCC2-related diseases beyond classic Coffin-Siris syndrome.

## Abstract

Coffin‐Siris syndrome (CSS) is a rare, clinically and genetically heterogeneous disorder characterized by coarse facial features, microcephaly, intellectual disability (ID), developmental delay (DD), and hypo/aplastic digital nails and phalanges, typically of the 5th digit. CSS is an autosomal dominant disease resulting from mutations in genes encoding components of BRG1/BRM‐associated factor (BAF) chromatin remodeling complexes. More than 300 CSS patients have been reported with variants in genes in the BAF pathway. Recently, patients carrying SMARCC2 variants have been reported to be associated with CSS8. However, as the number of cases increases, many patients do not exhibit the representative clinical symptoms of CSS. Additional case reports and clinical studies will contribute to a redefinition of SMARCC2‐related disorders.

In this research, three patients with SMARCC2‐related disorders from China were recruited. Genomic DNA was extracted from the peripheral blood leukocytes of these patients' parents and other family members, and then subjected to whole‐exome sequencing as well as Sanger sequencing.

In the present study, two de novo variants (c.1311‐3C>G, c.347G>A (p.Arg116His)) and a novel de novo variant (c.346C>T (p.Arg116Cys)) in the SMARCC2 gene were detected in three patients with neurodevelopmental disorders by whole exome sequencing. The clinical presentation of our patients supports a redefinition of SMARCC2‐related diseases, which include mild to moderate DD, mild ID, facial dysmorphism, mild speech delay, hypotonia, feeding difficulties, brain abnormalities, attention deficit hyperactivity disorder (ADHD), and autistic behaviors. Furthermore, both the type of variant and its specific location may be contributing factors influencing the clinical outcomes.

Our study expands the genetic spectrum of SMARCC2 variants and detailed genotypic and phenotypic descriptions are important for the diagnosis of SMARCC2‐related disease and accurate clinical management.

In this article, we investigate the pathogenesis of three unrelated Chinese children who exhibited mild to moderate developmental delay, mild intellectual disability, facial dysmorphism, mild speech delay, hypotonia, feeding difficulties, brain abnormalities, attention deficit hyperactivity disorder (ADHD), and autistic behaviors. Furthermore, both the type of variant and its specific location may be contributing factors influencing the clinical outcomes. Our study expands the genetic spectrum of SMARCC2 variants, and detailed genotypic and phenotypic descriptions are important for the diagnosis of SMARCC2‐related disease and accurate clinical management.