Purpose of review: To report on the expanding clinical and immunological spectrum associated with ribonuclease mitochondrial RNA-processing mutations and to review the cellular and molecular mechanisms involved in the pathophysiology of cartilage-hair hypoplasia (CHH) and related disorders in humans.
Recent findings: Different types of mutations are associated with skeletal or extraskeletal manifestations of CHH, respectively. In particular, severe immunodeficiency is mostly associated with mutations that alter cyclin B2 mRNA cleavage and thus are likely to reflect disturbances in cell cycle control. The first cases of ribonuclease mitochondrial RNA-processing mutations with severe immunodeficiency, but no skeletal abnormalities, have been identified.
Summary: Abnormalities of ribosome biogenesis have been shown to cause distinct bone marrow failure syndromes, including CHH. However, the specific role of ribosomal and extraribosomal defects in the pathophysiology of the various phenotypic features of CHH remains undefined. Development of suitable animal models is needed to address this important issue.