A Ribosomopathy Reveals Decoding Defective Ribosomes Driving Human Dysmorphism.

ABSTRACT: Ribosomal protein (RP) gene mutations, mostly associated with inherited or acquired bone marrow failure, are believed to drive disease by slowing the rate of protein synthesis. Here de novo missense mutations in the RPS23 gene, which codes for uS12, are reported in two unrelated individuals with microcephaly, hearing loss, and overlapping dysmorphic features. One individual additionally presents with intellectual disability and autism spectrum disorder. The amino acid substitutions lie in two highly conserved loop regions of uS12 with known roles in maintaining the accuracy of mRNA codon translation. Primary cells revealed one substitution severely impaired OGFOD1-dependent hydroxylation of a neighboring proline residue resulting in 40S ribosomal subunits that were blocked from polysome fo

SUBMITTER: Paolini NA 

PROVIDER: S-EPMC5339345 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature