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Defective DcpS Decapping Manifests in Creatine Deficiency Syndrome and Neurological impairment

GSE274722 Homo sapiens Expression profiling by high throughput sequencing 6 samples Submitted 2025/05/30 Platform GPL24676
Summary
Biallelic mutations in the DCPS gene that disrupt the decapping activity of the DcpS scavenger decapping enzyme lead to neurodevelopmental deficiencies and intellectual disability. However, how the neurogenesis defects arise in these individuals remains unknown. Here we show that cells derived from DCPS mutant individuals have a metabolic deficiency in their creatine biosynthetic pathway. The cells possess reduced levels of creatine and a corresponding elevation of the creatine precursor, guanidinoacetate (GAA), due to reduced levels of guanidinoacetate methyltransferase mRNA and protein. Importantly, the compromised neurogenesis as well as neurite outgrowth observed in DcpS mutant induced pluripotent stem cell differentiation into neurons was reversed upon supplementation of creatine monohydrate into the culture medium. These findings suggest creatine deficiency as the underlying etiology of the neurogenetic defect in DcpS mutant cells and a potential driver of the neurological deficienciesin affected individuals.
Published in
Creatine mitigates neurogenesis impairment caused by defective DcpS decapping
Yang J, Palsule G, Jiao X et al. · Scientific reports 2025 · PMID 40410278 · doi:10.1038/s41598-025-02961-5
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Also filed as BioProject PRJNA1147714 and SRA study SRP526097. Searching any of these in the dataset finder brings you back here.

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