De novo variants in the PRPF8 gene have been identified in ASD probands, including a de novo splice-site variant in a proband from a simplex family and several de novo missense variants (Iossifov et al., 2014; Krumm et al., 2015; Sanders et al., 2015; Yuen et al., 2017; Takata et al., 2018; da Silva Montenegro et al., 2020). Meta-analysis of 13,754 previously published NDD probands and 2,299 controls in da Silva Montenegro et al., 2020 identified six additional patients with validated de novo variants in PRPF8, and a comparison of de novo variants with a previously established mutational rate model found that PRPF8 showed nominal significance before multiple test correction (P = 0.039, P-value adjusted = 0.079, binomial test). O'Grady et al., 2022 reported 12 individuals with heterozygous variants in PRPF8 presenting with a neurodevelopmental syndrome characterized by some degree of intellectual disability or developmental delay, hypotonia, structural cardiac abnormalities, feeding difficulties, behavioral issues, abnormal brain MRI, and dysmorphic features; a diagnosis of ASD was made in approximately half of the individuals in this study.
Molecular Function
Pre-mRNA splicing occurs in 2 sequential transesterification steps. The protein encoded by this gene is a component of both U2- and U12-dependent spliceosomes, and found to be essential for the catalytic step II in pre-mRNA splicing process. It contains several WD repeats, which function in protein-protein interactions. This protein has a sequence similarity to yeast Prp8 protein. This gene is a candidate gene for autosomal dominant retinitis pigmentosa (retinitis pigmentosa 13; OMIM 600059).
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
The contribution of de novo coding mutations to autism spectrum disorder
