Research Information System
Journal of Pediatric Endocrinology and Metabolism, 2026 (SCI-Expanded, Scopus)
Objectives: NSUN3 encodes a mitochondrial RNA methyltransferase responsible for cytosine methylation at the tRNA wobble base, which plays a role in the regulation of mitochondrial translation. Variants in NSUN3 lead to impaired oxidative phosphorylation resulting in multisystem involvement. Reported cases to date have described developmental delay, hypotonia, optic atrophy and neurological involvement. Cardiac manifestations, however, have not yet been clearly associated with NSUN3 deficiency. Here, we report hypertrophic cardiomyopathy (HCM) as a new clinical feature and the long-term follow-up of our case, further expanding the phenotype of NSUN3-related disease. Case presentation: An 18-year-old girl was referred for visual loss, progressive fatigue, muscle weakness and HCM. Initial symptoms started as hypotonia in infancy and proceeded with developmental delay, reduced visual acuity and chest pain. At the age 15 years, she was diagnosed with HCM. Cardiac magnetic resonance imaging showed concentric left ventricular (LV) hypertrophy with septal thickness measuring up to 20 mm, LV ejection fraction was preserved (70 %). Whole exome sequencing identified a homozygous likely pathogenic variant in the NSUN3 gene: NM_022072.5: c.465dup (p.Gly156ArgfsTer6), for which both parents were found to be heterozygous carriers. Conclusions: To our knowledge, this is the first reported case of NSUN3-related mitochondrial disease with HCM. An increasing number of reported cases will likely contribute to a more comprehensive understanding of the clinical phenotype and genotype–phenotype correlations.