Ceraolo Graziana, Spoto Giulia, Butera Ambra, Spanò Maria, Vinci Mirella, Vitello Girolamo Aurelio, Musumeci Antonino, Calì Francesco, Nicotera Antonio Gennaro, Di Rosa Gabriella
Unit of Child Neurology and Psychiatry, Department of Human Pathology of the Adult and Developmental Age "Gaetano Barresi", University of Messina, Messina, Italy.
Unit of Child Neurology and Psychiatry, Department of Biomedical Sciences, Dental Sciences & Morpho-Functional Imaging, University of Messina, Messina, Italy.
Am J Med Genet B Neuropsychiatr Genet. 2025 Apr;198(3):e33015. doi: 10.1002/ajmg.b.33015. Epub 2024 Oct 23.
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.
TRMT10A与一种以早发性糖尿病、小头畸形、癫痫和智力残疾为特征的综合征有关。我们报告了一例患者，该患者表现为痉挛性共济失调性截瘫和Dandy-Walker变异型，与TRMT10A基因中一个导致疾病的纯合c.421-1G＞A变异相关，该变异影响一个典型的剪接位点。这种突变破坏了“依赖SAM的甲基转移酶TRM10型结构域”，该结构域参与甲基化和S-腺苷甲硫氨酸代谢生物学过程，对线粒体和葡萄糖代谢至关重要。我们患者明显的神经受累增强了TRMT10A在脑发育中的作用，提示TRMT10A变异与显性神经表型之间可能存在关联。该病例扩展了TRMT10A综合征的临床谱，突出了在评估脑/小脑畸形和痉挛性共济失调性截瘫患者时考虑该基因的重要性。有必要进行进一步研究以阐明潜在的致病机制和潜在的治疗意义。
