CAKUT variants in <i>PRPF8, DYRK2</i>, and <i>CEP78</i>: implications for splicing and ciliogenesis.

ABSTRACT:

Introduction

Congenital anomalies of the kidney and urinary tract (CAKUT) are the leading cause of chronic kidney disease in children and young adults. Although over 50 monogenic causes have been identified, many remain unresolved. PRPF8 is a core spliceosome component, essential for pre-mRNA splicing, and further localizes to the distal mother centriole to promote ciliogenesis.

Methods

We performed trio exome sequencing in 208 CAKUT families and identified strong variants in PRPF8 and the EDD-DYRK2-DDB1^VprBP complex. Functional validation included splicing assays in yeast (Saccharomyces cerevisiae), Sonic hedgehog (Shh) signaling in RPE-1 cells, co-immunoprecipitation for protein complex assembly, and in situ hybridization in mouse embryos. Protein interac

SUBMITTER: Merz LM 

PROVIDER: S-EPMC12330721 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature