Variants of the RPL13 gene have for the first time been identified as genetic cause of a rare skeletal disorder. In the American Journal of Human Genetics, the authors describe a role of the RPL13 protein in bone development. RPL13 is a ribosomal protein and a component of the larger of the two ribosomal subunits. Ribosomes, the molecular machines responsible for protein synthesis, consist of a small 40S unit and a larger 60S unit. Together, they are composed of four ribosomal RNA species and about 80 structurally distinct proteins. So far, variants in ribosomal genes have been associated with Diamond-Blackfan anemia, a rare congenital bone marrow disorder, and with isolated congenital asplenia.

Now the current study reports on four de novo variants of RPL13 discovered to underlie a rare bone disorder in four patients with severe short stature. In further functional analyses, the researchers showed that, in contrast to observations from Diamond-Blackfan anemia, there was no significant disturbance in pre-rRNA processing. The altered protein showed stable expression and integration into 60S subunits. They found, however, indications for changes in translation dynamics. Also, elevated RPL13 levels were present in chrondocytes and osteoblasts in the mouse.