Naturally occurring splice variants dissect the functional domains of BHC80 and emphasize the need for RNA analysis.
ID (intellectual disability)
PHF21A (plant homeodomain finger protein 21A)
RNA splicing
overgrowth
transcriptome
Journal
American journal of medical genetics. Part A
ISSN: 1552-4833
Titre abrégé: Am J Med Genet A
Pays: United States
ID NLM: 101235741
Informations de publication
Date de publication:
24 Jan 2024
24 Jan 2024
Historique:
revised:
04
01
2024
received:
23
11
2023
accepted:
12
01
2024
medline:
24
1
2024
pubmed:
24
1
2024
entrez:
24
1
2024
Statut:
aheadofprint
Résumé
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.
Identifiants
pubmed: 38264805
doi: 10.1002/ajmg.a.63548
doi:
Types de publication
Case Reports
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : BC Children's Hospital Foundation
Informations de copyright
© 2024 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.
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