Hypomorphic variant in TRNT1 induces a milder autoinflammatory disease with congenital cataracts and impaired sexual development.

Abstract

Dear Editor, tRNA nucleotidyltransferase-1 (TRNT1) is a nucleotidyltransferase of ubiquitous expression, implicated in the maturation of cytosolic and mitochondrial tRNA. Its activity is the addition of a conserved CCA trinucleotide sequence of the 3′ terminus that acts as the binding site of the amino acid in the tRNA molecule [1]. In 2014, Chakraborty et al. [2] reported that bi-allelic loss of function variants in TRNT1 were the cause of sideroblastic anaemia, B cell immunodeficiency, periodic fevers and developmental delay (SIFD) syndrome. This severe clinical phenotype had been described only a year before in 12 patients who shared these common features, with unknown genetic aetiology [3]. Seven patients had died before 14 years of age and the most severely affected did not live beyond the third year of life. Among the surviving individuals, only one had reached adulthood at the time of publication, presenting...