Recurrent de novo variants in the spliceosomal factor CRNKL1 are associated with severe microcephaly and pontocerebellar hypoplasia with seizures.

ABSTRACT: Splicing is a complex process that is required to create the transcriptomic diversity needed for specialized functions in higher eukaryotes. The spliceosome contains more than 100 proteins and RNA molecules, which coordinate this dynamic process. Despite the ubiquity of splicing, pathogenic variants in spliceosomal components often cause a tissue-specific phenotype, hinting at further complexities that are not yet fully understood. We have identified a cohort of ten families with de novo missense variants in a spliceosomal component, CRNKL1, where nine individuals harbor one of two missense variants that both affect the same amino acid, Arg267. All affected individuals share a common and specific phenotype: profound pre- and post-natal microcephaly, with pontocerebellar hypoplasia, seizure

SUBMITTER: Ray Das S 

PROVIDER: S-EPMC12256911 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature