JOURNAL ARTICLE
REVIEW
Add like
Add dislike
Add to saved papers

Germline variants in SMARCB1 and other members of the BAF chromatin-remodeling complex across human disease entities: a meta-analysis.

Germline variants that affect function are found in seven genes of the BAF chromatin-remodeling complex. They are linked to a broad range of diseases that, according to the gene affected, range from non-syndromic or syndromic neurodevelopmental disorders to low-grade tumors and malignancies. In the current meta-analysis, we evaluate genetic and clinical data from more than 400 families and 577 patients affected by BAF germline alterations. We focus on SMARCB1, including 43 unpublished patients from the EU-RHAB registry and our institution. For this gene, we further demonstrate whole gene as well as exon deletions and truncating variants to be associated with malignancy and early-onset disease. In contrast, non-truncating variants are associated with non-malignant disorders, such as Coffin-Siris syndrome or late-onset tumors like schwannoma or meningioma (p < 0.0001). SMARCB1 germline variants are distributed across the gene with variants in exons 1, 2, 8, and 9 being associated with low-grade entities, and single-nucleotide variants or indels outside of exon 9 that appear in patients with malignancies (p < 0.001). We attribute variants in specific BAF genes to certain disease entities. Finally, single-nucleotide variants and indels are sometimes detected in the healthy relatives of tumor patients, while Coffin-Siris syndrome and Nicolaides-Baraitser syndrome generally seem to appear de novo. Our findings add further information on the genotype-phenotype association of germline variants detected in genes of the BAF complex. Functional studies are urgently needed for a deeper understanding of BAF-related disorders and may take advantage from the comprehensive information gathered in this article.

Full text links

We have located links that may give you full text access.
Can't access the paper?
Try logging in through your university/institutional subscription. For a smoother one-click institutional access experience, please use our mobile app.

For the best experience, use the Read mobile app

Mobile app image

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app

All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

By using this service, you agree to our terms of use and privacy policy.

Your Privacy Choices Toggle icon

You can now claim free CME credits for this literature searchClaim now

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app