title: Reduced thymic output, cell cycle abnormalities, and increased apoptosis of T lymphocytes in patients with cartilage-hair hypoplasia.
abstract: BACKGROUND
  Cartilage-hair hypoplasia (CHH) is characterized by metaphyseal dysplasia, bone marrow failure, increased risk of malignancies, and a variable degree of immunodeficiency. CHH is caused by mutations in the RNA component of the mitochondrial RNA processing (RMRP) endoribonuclease gene, which is involved in ribosomal assembly, telomere function, and cell cycle control.
  
  
  OBJECTIVE
  We aimed to define thymic output and characterize immune function in a cohort of patients with molecularly defined CHH with and without associated clinical immunodeficiency.
  
  
  METHODS
  We studied the distribution of B and T lymphocytes (including recent thymic emigrants), in vitro lymphocyte proliferation, cell cycle, and apoptosis in 18 patients with CHH compared with controls.
  
  
  RESULTS
  Patients with CHH have a markedly reduced number of recent thymic emigrants, and their peripheral T cells show defects in cell cycle control and display increased apoptosis, resulting in poor proliferation on activation.
  
  
  CONCLUSIONS
  These data confirm that RMRP mutations result in significant defects of cell-mediated immunity and provide a link between the cellular phenotype and the immunodeficiency in CHH.
authors.affiliation: Division of Immunology and the Manton Center for Orphan Disease Research.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: de la Fuente
authors.affiliation: Division of Immunology and the Manton Center for Orphan Disease Research.
authors.forename: Mike
authors.initials: M
authors.lastname: Recher
authors.affiliation: Clinic for Special Children, Strasburg.
authors.forename: Nicholas L
authors.initials: NL
authors.lastname: Rider
authors.affiliation: Clinic for Special Children, Strasburg.|Department of Biology, Franklin and Marshall College, Lancaster.
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Strauss
authors.affiliation: Clinic for Special Children, Strasburg.|Department of Biology, Franklin and Marshall College, Lancaster.
authors.forename: D Holmes
authors.initials: DH
authors.lastname: Morton
authors.affiliation: Department of Pediatrics, National Jewish Health, Denver.
authors.forename: Margaret
authors.initials: M
authors.lastname: Adair
authors.affiliation: Division of Immunology and the Manton Center for Orphan Disease Research.
authors.forename: Francisco A
authors.initials: FA
authors.lastname: Bonilla
authors.affiliation: Department of Pediatrics, University of Washington School of Medicine and Seattle Children's Research Institute.
authors.forename: Hans D
authors.initials: HD
authors.lastname: Ochs
authors.affiliation: Department of Pediatrics, National Jewish Health, Denver.
authors.forename: Erwin W
authors.initials: EW
authors.lastname: Gelfand
authors.affiliation: Division of Immunology and the Manton Center for Orphan Disease Research.
authors.forename: Itai M
authors.initials: IM
authors.lastname: Pessach
authors.affiliation: Division of Immunology and the Manton Center for Orphan Disease Research.
authors.forename: Jolan E
authors.initials: JE
authors.lastname: Walter
authors.affiliation: Immunology Unit, Hospital Luis Calvo Mackenna, Santiago.
authors.forename: Alejandra
authors.initials: A
authors.lastname: King
authors.affiliation: "Angelo Nocivelli" Institute for Molecular Medicine and Department of Pediatrics, University of Brescia.
authors.forename: Silvia
authors.initials: S
authors.lastname: Giliani
authors.affiliation: Division of Hematology, Children's Hospital Boston.
authors.forename: Sung-Yun
authors.initials: SY
authors.lastname: Pai
authors.affiliation: Division of Immunology and the Manton Center for Orphan Disease Research.
authors.forename: Luigi D
authors.initials: LD
authors.lastname: Notarangelo
mesh_terms: D000293:Adolescent; D017209:Apoptosis / Q000276:immunology*; D002453:Cell Cycle / Q000276:immunology*; D002469:Cell Separation; D002648:Child; D002675:Child, Preschool; D005260:Female; D005434:Flow Cytometry; D005838:Genotype; D006197:Hair / Q000002:abnormalities / Q000276:immunology / Q000473:pathology; D006627:Hirschsprung Disease / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D007223:Infant; D008297:Male; D009154:Mutation; D010009:Osteochondrodysplasias / Q000151:congenital* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D010641:Phenotype; D016133:Polymerase Chain Reaction; D000081207:Primary Immunodeficiency Diseases; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology*; D055815:Young Adult
chemical_list: C544035:RMRP non-coding RNA, human; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated