Small nuclear RNA genes in Mendelian disorders

Small nuclear RNA (snRNA) genes represent a class of non-protein-coding genes involved in the processing of pre-mRNAs of intron-containing genes. The human genome contains approximately 2,000 snRNA genes; the majority are pseudogenes, and only a small fraction are functional. These snRNAs undergo extensive post-transcriptional modifications, and, together with proteins and other snRNAs, form small nuclear ribonucleoproteins, which are components of the spliceosome. This Review discusses high-impact variants in 12 snRNA genes that cause Mendelian disorders with either autosomal dominant or recessive inheritance patterns. The associated phenotypes include mainly neurodevelopmental delay, developmental abnormalities and retinitis pigmentosa. The presumed consequences of these variants are presented on the basis of previous functional characterization of the corresponding snRNAs. It is anticipated that the understanding of both Mendelian and complex traits due to snRNAs will increase the diagnostic potential, partially explain penetrance and provide more therapeutic options.