A Novel Intronic Variant in the KH3 Domain of HNRNPK Leads to a Mild Form of Au-Kline Syndrome.

ABSTRACT: Despite the massive adoption of sequencing technologies, disease-specific diagnosis remains challenging, particularly for genes with highly homologous pseudogenes like HNRNPK. Pathogenic HNRNPK variants cause Au-Kline syndrome (AKS), a neurodevelopmental disorder with malformations and distinctive facial features. We validated a novel de novo HNRNPK intronic variant (c.1192-3 C>A, p.Leu398ValfsTer21) in a patient previously misdiagnosed with Kabuki Syndrome (KS). By combining sequencing, in vitro splicing assays, molecular modelling, and protein function analysis, we characterised the molecular defect. A unique DNA methylation (DNAm) signature was recently identified in AKS, with missense variants showing an intermediate DNAm pattern, suggesting an epi-genotype-phenotype correlation linked

SUBMITTER: Mingoia M 

PROVIDER: S-EPMC12501752 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature