Discover the groundbreaking research linking biallelic NAA60 variants to autosomal recessive primary familial brain calcifications, shedding new light on the genetic underpinnings of this rare condition.
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Biallelic NAA60 variants with impaired n-terminal acetylation capacity cause autosomal recessive primary familial brain calcifications.
Chelban et al., Nat Commun 2024
<!– DOI: 10.1038/s41467-024-46354-0 //–>
https://doi.org/10.1038/s41467-024-46354-0
This study identifies biallelic NAA60 variants as a new genetic cause for Primary Familial Brain Calcification (PFBC), a disorder marked by calcium deposits in the brain leading to movement disorders, psychiatric symptoms, and cognitive decline. Previously, PFBC had been linked to variants in six genes, but many patients lacked a genetic diagnosis. The research found that these NAA60 variants result in a loss-of-function, specifically affecting protein N-terminal (Nt)-acetylation activity. Importantly, the study demonstrates that the phosphate importer SLC20A2 is a substrate for NAA60 in vitro, and that loss of NAA60 reduces SLC20A2’s surface levels in cells, consequently decreasing extracellular phosphate uptake. This discovery not only adds NAA60 to the list of genes associated with PFBC but also offers insight into the biochemical mechanisms underlying the disease. It highlights the critical role of NAA60-mediated Nt-acetylation of transmembrane proteins in maintaining neurological health.