Naturally occurring splice variants dissect the functional domains of <scp>BHC80</scp> and emphasize the need for <scp>RNA</scp> analysis-Reference-Cited by-同舟云学术

Naturally occurring splice variants dissect the functional domains of BHC80 and emphasize the need for RNA analysis

Published:2024-01-24 Issue:6 Volume:194 Page:
ISSN:1552-4825
Container-title:American Journal of Medical Genetics Part A
language:en
Short-container-title:American J of Med Genetics Pt A

Author:

Hejla Duha¹,Huynh Stephanie²³,Samra Simran⁴⁵,Richmond Phillip A.⁴,Dalmann Joshua⁴,Del Bel Kate L.⁴,Byres Loryn⁴,Lehman Anna⁴,Turvey Stuart E.⁴,Boerkoel Cornelius F.²³^ORCID

Affiliation:

1. Department of Pediatrics University of British Columbia and Children's Hospital of British Columbia Vancouver British Columbia Canada

2. Provincial Medical Genetics Program B.C. Women's Hospital Vancouver British Columbia Canada

3. Department of Medical Genetics University of British Columbia Vancouver British Columbia Canada

4. The Rare Disease Discovery Hub, BC Children's Hospital Research Institute University of British Columbia and Children's Hospital of British Columbia Vancouver British Columbia Canada

5. Experimental Medicine Program, Department of Medicine University of British Columbia Vancouver British Columbia Canada

Abstract

AbstractPathogenic PHF21A variation causes PHF21A‐related neurodevelopmental disorders (NDDs). Although amorphic alleles, including haploinsufficiency, have been established as a disease mechanism, increasing evidence suggests that missense variants as well as frameshift variants extending the BHC80 carboxyl terminus also cause disease. Expanding on these, we report a proposita with intellectual disability and overgrowth and a novel de novo heterozygous PHF21A splice variant (NM_001352027.3:c.[153+1G>C];[=]) causing skipping of exon 6, which encodes an in‐frame BHC80 deletion (p.(Asn30_Gln51del)). This deletion disrupts a predicted leucine zipper domain and implicates this domain in BHC80 function and as a target of variation causing PHF21A‐related NDDs. This extension of understanding emphasizes the application of RNA analysis in precision genomic medicine practice.

Funder

BC Children’s Hospital Foundation

Publisher

Wiley

Link

https://onlinelibrary.wiley.com/doi/pdf/10.1002/ajmg.a.63548

Reference15 articles.

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