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

Pathogenic 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. © 2024 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.

Citation

Duha Hejla, Stephanie Huynh, Simran Samra, Phillip A Richmond, Joshua Dalmann, Kate L Del Bel, Loryn Byres, Anna Lehman, Stuart E Turvey, Cornelius F Boerkoel. Naturally occurring splice variants dissect the functional domains of BHC80 and emphasize the need for RNA analysis. American journal of medical genetics. Part A. 2024 Jun;194(6):e63548

Mesh Tags

PMID: 38264805

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