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. 2021 Jun 19;12(6):937.
doi: 10.3390/genes12060937.

Genotype-Phenotype Correlations in 208 Individuals with Coffin-Siris Syndrome

Ashley Vasko  1 , Theodore G Drivas  2   3 , Samantha A Schrier Vergano  4   5
Affiliations

Genotype-Phenotype Correlations in 208 Individuals with Coffin-Siris Syndrome

Ashley Vasko et al. Genes (Basel). .

Abstract

Coffin-Siris syndrome (CSS, MIM 135900) is a multi-system intellectual disability syndrome characterized by classic dysmorphic features, developmental delays, and organ system anomalies. Genes in the BRG1(BRM)-associated factors (BAF, Brahma associated factor) complex have been shown to be causative, including ARID1A, ARID1B, ARID2, DPF2, SMARCA4, SMARCB1, SMARCC2, SMARCE1, SOX11, and SOX4. In order to describe more robust genotype-phenotype correlations, we collected data from 208 individuals from the CSS/BAF complex registry with pathogenic variants in seven of these genes. Data were organized into cohorts by affected gene, comparing genotype groups across a number of binary and quantitative phenotypes. We determined that, while numerous phenotypes are seen in individuals with variants in the BAF complex, hypotonia, hypertrichosis, sparse scalp hair, and hypoplasia of the distal phalanx are still some of the most common features. It has been previously proposed that individuals with ARID-related variants are thought to have more learning and developmental struggles, and individuals with SMARC-related variants, while they also have developmental delay, tend to have more severe organ-related complications. SOX-related variants also have developmental differences and organ-related complications but are most associated with neurodevelopmental differences. While these generalizations still overall hold true, we have found that all individuals with BAF-related conditions are at risk of many aspects of the phenotype, and management and surveillance should be broad.

Keywords: BAF complex; Coffin-Siris syndrome; genotype-phenotype.

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Conflict of interest statement

Vergano is a medical advisor to the Coffin-Siris Syndrome Foundation. The remaining authors declare no conflict of interest.

Figures

Figure 1
Figure 1
(A). Qualitative phenotypes in individuals with variants in the BAF complex. (B–D). Quantitative phenotypes in individuals with variants in the BAF complex.
Figure 1
Figure 1
(A). Qualitative phenotypes in individuals with variants in the BAF complex. (B–D). Quantitative phenotypes in individuals with variants in the BAF complex.
See this image and copyright information in PMC

References

    1. Zawerton A., Yao B., Yeager P., Pippucci T., Haseeb A., Smith J., Wischmann L., Kühl S., Dean J., Pilz D., et al. De novo SOX4 variants cause a neurodevelopmental disease associated with mild dysmorphism. Am. J. Hum. Genet. 2019;104:246–259. doi: 10.1016/j.ajhg.2018.12.014. - DOI - PMC - PubMed
    1. Bögershausen N., Wollnik B. Mutations Landscapes and Phenotypic Spectrum of SWI/SNF-Related Intellectual Disability Disorders. Front. Mol. Neurosci. 2018;11:252. doi: 10.3389/fnmol.2018.00252. - DOI - PMC - PubMed
    1. Wieczorek D., Bogershausen N., Beleggia F., Steiner-Haldenstatt S., Pohl E., Li Y., Milz E., Martin M., Thiele H., Altmuller J., et al. A comprehensive molecular study on Coffin-Siris and Nicolaides-Baraitser syndromes identifies a broad molecular and clinical spectrum converging on altered chromatin remodeling. Hum. Mol. Genet. 2013;22:5121–5135. doi: 10.1093/hmg/ddt366. - DOI - PubMed
    1. Kosho T., Okamoto N. Coffin-Siris Syndrome International Collaborators. Genotype-phenotype correlation of Coffin-Siris syndrome caused by mutations in SMARCB1, SMARCA4, SMARCE1, and ARID1A. Am. J. Med. Genet. C Semin. Med. Genet. 2014;166C:262–275. doi: 10.1002/ajmg.c.31407. - DOI - PubMed
    1. Santen G.W., Clayton-Smith J., The ARID1B-CSS Consortium The ARID1B phenotype: What we have learned so far. Am. J. Med. Genet. C Semin. Med. Genet. 2014;166C:276–289. doi: 10.1002/ajmg.c.31414. - DOI - PubMed

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