A novel mutation in SMARCB1 associated with adult Coffin-Siris syndrome and meningioma

Zhenglong Guo; Jie Bai; Yang Liu; Xianwei Zhang; Wenke Yang; Jinming Wang; Yuwei Zhang; Hai Xiao; Bingtao Hao; Shixiu Liao

doi:10.3724/abbs.2024204

A novel mutation in SMARCB1 associated with adult Coffin-Siris syndrome and meningioma

Acta Biochim Biophys Sin (Shanghai). 2024 Nov 13. doi: 10.3724/abbs.2024204. Online ahead of print.

Authors

Zhenglong Guo^{1

2}, Jie Bai^{1

2}, Yang Liu^{1

2}, Xianwei Zhang^{1

2}, Wenke Yang^{1

2}, Jinming Wang^{1

2}, Yuwei Zhang^{1

2}, Hai Xiao^{1

2}, Bingtao Hao^{1

3

4}, Shixiu Liao^{1

2}

Affiliations

¹ Henan Provincial Key Laboratory of Genetic Diseases and Functional Genomics, Medical Genetics Institute of Henan Province, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou 450000, China.
² School of Medicine, People's Hospital of Henan University, Henan University, Zhengzhou 450000, China.
³ Department of Immunology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China.
⁴ Henan Eye Institute, Henan Academy of Innovations in Medical Science, Zhengzhou 450000, China.

PMID: 39563460
DOI: 10.3724/abbs.2024204

Abstract

SMARCB1 encodes a core subunit of the SWI/SNF chromatin remodeling complex, which plays a crucial role in the regulation of gene expression. Germline mutations in the SMARCB1 gene have been linked to early childhood Coffin-Siris syndrome type 3 (CSS3), a rare congenital malformation syndrome characterized by severe developmental delay and intellectual disability. In this study, we report a family of two adult CSS3 patients with a novel missense SMARCB1 mutation (c.1091A>C, p.Lys364Thr) identified through whole-exome sequencing (WES). Both patients exhibit selective difficulties in verbal learning and experience language delays. Additionally, the development of meningioma is confirmed in one of the patients. Mechanistic studies suggest that this missense mutation may abnormally activate the MAPK signaling pathway, which is implicated in the pathogenesis of tumor progression and neurodevelopmental disorders. This is the first reported case of a germline mutation in the SMARCB1 gene associated with both CSS3 and meningioma, thereby expanding the phenotypic spectrum of SMARCB1-related disorders.

Keywords: SMARCB1; SWI/SNF; meningioma; neurodevelopmental disorder.