title: Cartilage-hair hypoplasia: molecular basis and heterogeneity of the immunological phenotype.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Immunology, Children's Hospital Boston, Boston, Massachusetts 02115, USA. luigi.notarangelo@childrens.harvard.edu
authors.forename: Luigi D
authors.initials: LD
authors.lastname: Notarangelo
authors.forename: Chaim M
authors.initials: CM
authors.lastname: Roifman
authors.forename: Silvia
authors.initials: S
authors.lastname: Giliani
mesh_terms: D002356:Cartilage / Q000378:metabolism* / Q000473:pathology; D002357:Cartilage Diseases / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D019926:Cyclin B / Q000235:genetics* / Q000378:metabolism; D056765:Cyclin B2; D004720:Endonucleases / Q000276:immunology / Q000378:metabolism*; D020022:Genetic Predisposition to Disease; D006197:Hair / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D006965:Hyperplasia / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D008928:Mitochondria / Q000201:enzymology / Q000235:genetics; D009154:Mutation; D010641:Phenotype; D012322:RNA Precursors / Q000235:genetics / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional / Q000187:drug effects / Q000235:genetics
chemical_list: C503758:CCNB2 protein, human; D019926:Cyclin B; D056765:Cyclin B2; D012322:RNA Precursors; D004720:Endonucleases