Elp2 mutations perturb the epitranscriptome and lead to a complex neurodevelopmental phenotype.

ABSTRACT: Intellectual disability (ID) and autism spectrum disorder (ASD) are the most common neurodevelopmental disorders and are characterized by substantial impairment in intellectual and adaptive functioning, with their genetic and molecular basis remaining largely unknown. Here, we identify biallelic variants in the gene encoding one of the Elongator complex subunits, ELP2, in patients with ID and ASD. Modelling the variants in mice recapitulates the patient features, with brain imaging and tractography analysis revealing microcephaly, loss of white matter tract integrity and an aberrant functional connectome. We show that the Elp2 mutations negatively impact the activity of the complex and its function in translation via tRNA modification. Further, we elucidate that the mutations perturb prote

SUBMITTER: Kojic M 

PROVIDER: S-EPMC8113450 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature