Null and missense mutations of ERI1 cause a recessive phenotypic dichotomy in humans

Roles of ribosomal RNA in health and disease

“…Similarly, this patient presented with limb abnormalities and intellectual disabilities, strengthening the case that ERI1 loss was the disease-causing mutation in the previous case. Finally, a recent study contrasts clinical manifestations in patients with either missense variants or bi-allelic null mutations in ERI1 (Guo et al, 2023). Patients with missense variants tend to have major skeletal defects known as severe spondyloepimetaphyseal dysplasia (SEMD), while those with biallelic null mutations suffer from much milder skeletal malformations and intellectual disabilities.…”

“…Patients with missense variants tend to have major skeletal defects known as severe spondyloepimetaphyseal dysplasia (SEMD), while those with biallelic null mutations suffer from much milder skeletal malformations and intellectual disabilities. Patients with ERI1 mutations exhibit defective processing of the 3′-end of 5.8S rRNA, as well as accumulating replication-dependent histone mRNAs (Guo et al, 2023). While these recent cases strongly implicate ERI1 in disease, the cause of these diseases is not known.…”