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Review
. 2025 Apr;198(3):e33015.
doi: 10.1002/ajmg.b.33015. Epub 2024 Oct 23.

New Insights Into TRMT10A Syndrome: Case Report and Literature Review

Graziana Ceraolo  1 , Giulia Spoto  2 , Ambra Butera  1   3 , Maria Spanò  4 , Mirella Vinci  5 , Girolamo Aurelio Vitello  5 , Antonino Musumeci  5 , Francesco Calì  5 , Antonio Gennaro Nicotera  4 , Gabriella Di Rosa  2
Affiliations
Review

New Insights Into TRMT10A Syndrome: Case Report and Literature Review

Graziana Ceraolo et al. Am J Med Genet B Neuropsychiatr Genet. 2025 Apr.

Abstract

TRMT10A is related to a syndrome characterized by early-onset diabetes mellitus, microcephaly, epilepsy, and intellectual disability. We report a case of a patient showing spastic-ataxic paraparesis and Dandy-Walker variant associated with a causative homozygous c.421-1G > A variant in the TRMT10A gene, affecting a canonical splicing site. This mutation disrupts the "SAM-dependent methyltransferase TRM10-type domain", which is implicated in methylation and S-adenosylmethionine metabolic biological processes, crucial for mitochondrial and glucose metabolism. The prominent neurological involvement of our patient enhances the implication of TRMT10A in the brain development, suggesting a potential association between TRMT10A variants and dominant neurological phenotypes. This case expands the clinical spectrum of TRMT10A syndrome highlighting the importance of considering this gene in the evaluation of patients with brain/cerebellar malformations and spastic-ataxic paraparesis. Further research is warranted to elucidate the underlying pathogenic mechanisms and potential therapeutic implications.

Keywords: Dandy–Walker variant; TRMT10A; intellectual disability; pediatric neurology; spastic–ataxic paraparesis.

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