An IMPDH2 variant associated with neurodevelopmental disorder disrupts purine biosynthesis and somitogenesis.

ABSTRACT: IMP dehydrogenase (IMPDH) controls a key regulatory node in purine biosynthesis. Gain-of-function mutations in human IMPDH2 are associated with neurodevelopmental disorders and neuromuscular symptoms including dystonia, but the developmental mechanisms underlying these defects are unknown. We previously showed that these mutants are insensitive to GTP inhibition and hypothesized that their hyperactivity would affect nucleotide metabolism in vivo. Here, we characterize the metabolic and developmental consequences of the neurodevelopmental disorder-associated IMPDH2 mutant, S160del, in Xenopus tropicalis. We show that expressing S160del but not WT human IMPDH2 disrupts purine pools and somitogenesis in the developing tadpole. We also show that S160del disrupts in vivo IM

SUBMITTER: O'Neill AG 

PROVIDER: S-EPMC12248025 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature