Relevance to Autism

Trio whole-exome sequencing of 173 children diagnosed with developmental delay/intellectual disability from China in Li et al., 2024 identified a de novo nonsense variant in the PUF60 gene in a a male patient presenting with autism spectrum disorder, speech delay, short stature, and spine malformation. Additional de novo variants in the PUF60 gene, including a de novo loss-of-function variant and two de novo missense variants (one of which was predicted to be deleterious by CADD, REVEL, and MPC), were previously reported in ASD probands from the Autism Sequencing Consortium and the SPARK cohort (De Rubeis et al., 2014; Zhou et al., 2022). Heterozygous variants or contiguous gene deletions affecting PUF60 are also responsible for Verheij syndrome (OMIM 615583), a disorder characterized by characterized by growth retardation, delayed psychomotor development, dysmorphic facial features, and skeletal (mainly vertebral) abnormalities; 2/5 individuals with PUF60 variants described in El Chehadeh et al., 2016 were reported to have autism spectrum disorder, while 1/12 individuals with PUF60 variants described in Low et al., 2017 was reported to have stereotypies.

Molecular Function

This gene encodes a nucleic acid-binding protein that plays a role in a variety of nuclear processes, including pre-mRNA splicing and transcriptional regulation. The encoded protein forms a complex with the far upstream DNA element (FUSE) and FUSE-binding protein at the myelocytomatosis oncogene (MYC) promoter. This complex represses MYC transcription through the core-TFIIH basal transcription factor.

External Links

References