ADARB1 mutations and RNA editing, a cause of a distinctive form of severe developmental and epileptic encephalopathy (DEE) ?
A new study published in Journal of Medical Genetics identified biallelic ADARB1 missense and deletion variants, within three children (from two consanguineous families) who express global developmental delay, intractable early infantile-onset seizures, microcephaly, severe-to-profound intellectual disability, axial hypotonia and progressive appendicular spasticity. The deletion variant leads to a loss of function in enzyme (from an incorrect splicing resulting in frameshift with a premature stop codon) who catalyse a RNA editing molecule. The missense variant leads to a severe impairment of the enzymatic activity, as showed by in vitro RNA editing assays (with transiently transfected cells). These data support the pathogenic role of these variants as the cause of a distinctive form of DEE, reinforcing the importance of RNA editing in brain function and development.