SMG9 mutation causes intellectual disability, confirming a role for nonsense-mediated decay components in neurocognitive development
A new study published in the European Journal of Human Genetics identified bi-allelic missense variant in the SMG9 gene (encoding a regulatory subunit of the mRNA nonsense-mediated decay -NMD- machinery), within five individuals (from three unrelated families) who express with intellectual disability (mild to moderate), intention tremor, pyramidal signs, dyspraxia, and ocular manifestations. RNA sequencing and differential gene expression analysis suggest that normal SMG9 function may be involved in transcriptional regulation without affecting nonsense mRNA-induced NMD. The mutation identified causes a neurodevelopmental disorder and impacts gene expression. NMD components have roles beyond aberrant mRNA degradation that are crucial for neurocognitive development.
- Eur J Hum Genet . 2022 May;30(5):619-627