Retinitis Pigmentosa and erythrocytic microcytosis related to hypomorphic variants in the TRNT1 gene

INTRODUCTION: The tRNA Nucleotidyl Transferase 1 (TRNT1) gene encodes an enzyme that adds a trinucleotide sequence (CCA) to the 3'-end of transfer RNA. Biallelic pathogenic TRNT1 variants are associated with a multisystem disorder featuring sideroblastic anaemia, B-cell immunodeficiency, periodic fevers and developmental delay. More recently, hypomorphic TRNT1 variants have been linked to a milder phenotype involving retinitis pigmentosa (RP) and erythrocytic microcytosis. METHODS: We report a novel case of TRNT1-related RP associated with erythrocytic microcytosis. Multimodal retinal imaging and electrodiagnostic testing were used to assess the clinical phenotype. Genetic testing was performed using whole genome sequencing and in silico analysis tools assessed variant pathogenicity. RESULTS: We describe a 13-year-old female with RP, cystoid macular oedema, optic nerve head drusen, and erythrocytic microcytosis. Aged 18, she experienced two unexplained tonic-clonic seizures. Genetic testing showed compound heterozygosity for c.1252dup p.(Ser418fs) and c.193G>C p.(Ala65Pro) variants in TRNT1. DISCUSSION: We report the fourth case of TRNT1-related RP with erythrocytic microcytosis, with a hypomorphic TRNT1 variant being in trans with a truncating variant. The significance of the seizures in our patient remains unclear. These findings contribute further to the current knowledge regarding the phenotypic spectrum associated with TRNT1.