<i>De novo</i> variants in the non-coding spliceosomal snRNA gene <i>RNU4-2</i> are a frequent cause of syndromic neurodevelopmental disorders.

ABSTRACT: Around 60% of individuals with neurodevelopmental disorders (NDD) remain undiagnosed after comprehensive genetic testing, primarily of protein-coding genes¹. Increasingly, large genome-sequenced cohorts are improving our ability to discover new diagnoses in the non-coding genome. Here, we identify the non-coding RNA RNU4-2 as a novel syndromic NDD gene. RNU4-2 encodes the U4 small nuclear RNA (snRNA), which is a critical component of the U4/U6.U5 tri-snRNP complex of the major spliceosome². We identify an 18 bp region of RNU4-2 mapping to two structural elements in the U4/U6 snRNA duplex (the T-loop and Stem III) that is severely depleted of variation in the general population, but in which we identify heterozygous variants in 119 individuals with

SUBMITTER: Chen Y 

PROVIDER: S-EPMC11030480 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature