The DNA methyltransferase complex conundrum: novel DNA methyltransferase 1 mutation in an Indian patient with dementia and sensory neural hearing loss on a background of long-standing psychosis.

Abstract

Epigenetic alterations, like DNA methylation, are increasingly recognised as integral to the development of both neurological and psychiatric disorders. Mutations in the DNA methyltransferase 1 (DNMT1) gene have also been linked to specific neurodegenerative syndromes. Despite these advances, when and how these alterations influence disease expression remains to be understood. This report highlights a novel heterozygous missense mutation in exon 30 of the DNMT1 gene that was detected in a middle-aged lady who presented with early-onset dementia on a background of long-standing psychosis with depression and neuroleptic sensitivity. This case expands the phenotypic spectrum associated with DNMT1 mutations and highlights the potential value of genetic testing in evaluating atypical neuropsychiatric presentations. The phenotypic complexity highlights the critical need for further research to elucidate the mechanistic links between DNMT1 mutations and neuropsychiatric disease, paving the way for targeted therapeutic interventions.