title: Variable phenotype of severe immunodeficiencies associated with RMRP gene mutations.
abstract: OBJECTIVE
  Mutations in RMRP primarily give rise to Cartilage Hair Hypoplasia (CHH), a highly diverse skeletal disorder which can be associated with severe immunodeficiency. Increased availability of RMRP mutation screening has uncovered a number of infants with significant immunodeficiency but only mild or absent skeletal features. We surveyed the clinical and immunological phenotype of children who have undergone allogeneic haematopoietic stem cell transplantation for this condition in the UK.
  
  
  METHODS
  Thirteen patients with confirmed RMRP mutations underwent allogeneic stem cell transplantation (SCT) at two nationally commissioned centres using a variety of donors and conditioning regimens. Records were retrospectively reviewed.
  
  
  RESULTS
  Median time from clinical presentation to diagnosis was 12 months (range 1 to 276 months), with three infants diagnosed with severe combined immunodeficiency (SCID) without radiographical manifestations of CHH. A total of 17 allogeneic procedures were performed on 13 patients including two stem-cell top-ups. The median age at transplant was 32.4 months (range 1.5 to 125 months). Of the eleven surviving patients, median follow-up was 50 months (range 21.6 to 168 months).
  
  
  CONCLUSIONS
  RMRP mutations can cause short stature and significant immunodeficiency which can be corrected by allogeneic SCT and the diagnosis should be considered even in the absence of skeletal manifestations.
authors: Molecular and Cellular Immunology Section, Institute of Child Health, University College of London, London, UK, w.ip@ucl.ac.uk.
authors: Winnie
authors: W
authors: Ip
authors: H Bobby
authors: HB
authors: Gaspar
authors: Robert
authors: R
authors: Kleta
authors: Estelle
authors: E
authors: Chanudet
authors: Chiara
authors: C
authors: Bacchelli
authors: Alison
authors: A
authors: Pitts
authors: Zohreh
authors: Z
authors: Nademi
authors: E Graham
authors: EG
authors: Davies
authors: Mary A
authors: MA
authors: Slatter
authors: Persis
authors: P
authors: Amrolia
authors: Kanchan
authors: K
authors: Rao
authors: Paul
authors: P
authors: Veys
authors: Andrew R
authors: AR
authors: Gennery
authors: Waseem
authors: W
authors: Qasim
mesh_terms: D000483:Alleles; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006086:Graft vs Host Disease / Q000209:etiology; D006197:Hair / Q000002:abnormalities; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006627:Hirschsprung Disease / Q000175:diagnosis / Q000235:genetics; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000175:diagnosis* / Q000235:genetics* / Q000628:therapy; D016130:Immunophenotyping; D007223:Infant; D007231:Infant, Newborn; D016131:Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D008297:Male; D009154:Mutation; D010009:Osteochondrodysplasias / Q000151:congenital / Q000175:diagnosis / Q000235:genetics; D010641:Phenotype; D000081207:Primary Immunodeficiency Diseases; D062085:RNA, Long Noncoding / Q000235:genetics*; D012720:Severity of Illness Index; D035781:Siblings; D018183:Transplantation Chimera; D016896:Treatment Outcome
chemical_list: C544035:RMRP non-coding RNA, human; D062085:RNA, Long Noncoding