title: The importance of considering monogenic causes of autoimmunity: A somatic mutation in KRAS causing pediatric Rosai-Dorfman syndrome and systemic lupus erythematosus.
abstract: OBJECTIVE
  Clinicians need to be aware of the growing list of defined monogenic etiologies of autoimmune diseases. This is particularly relevant when evaluating children, as these rare monogenic forms of autoimmunity tend to present very early in life.
  
  
  RESULTS
  By harnessing the transformative power of next generation sequencing, we made the unifying diagnosis of RAS-associated autoimmune leukoproliferative disease (RALD), caused by the somatic gain-of-function p.G13C KRAS mutation, in a boy with the seemingly unrelated immune dysregulatory conditions of Rosai-Dorfman and systemic lupus erythematosus (SLE).
  
  
  CONCLUSIONS
  This case expands our understanding of the clinical phenotypes associated with the extremely rare condition of RALD, and emphasizes the importance of always considering the possibility of a monogenic cause for autoimmunity, particularly when the disease manifestations begin early in life and do not follow a typical clinical course.
authors.affiliation: Department of Pediatrics, British Columbia Children's Hospital, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Ragotte
authors.affiliation: Department of Pediatrics, British Columbia Children's Hospital, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Anita
authors.initials: A
authors.lastname: Dhanrajani
authors.affiliation: Bruins Pediatric Centre, Chilliwack General Hospital, Chilliwack, BC, Canada.
authors.forename: Julian
authors.initials: J
authors.lastname: Pleydell-Pearce
authors.affiliation: Department of Pediatrics, British Columbia Children's Hospital, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Kate L
authors.initials: KL
authors.lastname: Del Bel
authors.affiliation: Department of Medical Genetics, British Columbia Children's Hospital, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Maja
authors.initials: M
authors.lastname: Tarailo-Graovac
authors.affiliation: Department of Medical Genetics, British Columbia Children's Hospital, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Clara
authors.initials: C
authors.lastname: van Karnebeek
authors.affiliation: Department of Pathology and Laboratory Medicine, British Columbia Children's Hospital, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Jefferson
authors.initials: J
authors.lastname: Terry
authors.affiliation: Department of Pathology and Laboratory Medicine, British Columbia Children's Hospital, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Christof
authors.initials: C
authors.lastname: Senger
authors.affiliation: Department of Medical Genetics, British Columbia Children's Hospital, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Margaret L
authors.initials: ML
authors.lastname: McKinnon
authors.affiliation: Department of Pediatrics, British Columbia Children's Hospital, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Seear
authors.affiliation: Department of Pediatrics, British Columbia Children's Hospital, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Julie S
authors.initials: JS
authors.lastname: Prendiville
authors.affiliation: Department of Pediatrics, British Columbia Children's Hospital, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Lori B
authors.initials: LB
authors.lastname: Tucker
authors.affiliation: Department of Pediatrics, British Columbia Children's Hospital, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Kristin
authors.initials: K
authors.lastname: Houghton
authors.affiliation: Department of Pediatrics, British Columbia Children's Hospital, University of British Columbia, Vancouver, BC, Canada.
authors.forename: David A
authors.initials: DA
authors.lastname: Cabral
authors.affiliation: Department of Pediatrics, British Columbia Children's Hospital, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Jaime
authors.initials: J
authors.lastname: Guzman
authors.affiliation: Department of Pediatrics, British Columbia Children's Hospital, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Ross E
authors.initials: RE
authors.lastname: Petty
authors.affiliation: Department of Pediatrics, British Columbia Children's Hospital, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Kelly L
authors.initials: KL
authors.lastname: Brown
authors.affiliation: Department of Pediatrics, British Columbia Children's Hospital, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Jenny
authors.initials: J
authors.lastname: Tekano
authors.affiliation: Department of Pediatrics, British Columbia Children's Hospital, University of British Columbia, Vancouver, BC, Canada.
authors.forename: John
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Pediatrics, British Columbia Children's Hospital, University of British Columbia, Vancouver, BC, Canada. Electronic address: kmorishita@cw.bc.ca.
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Morishita
authors.affiliation: Department of Pediatrics, British Columbia Children's Hospital, University of British Columbia, Vancouver, BC, Canada. Electronic address: sturvey@cw.bc.ca.
authors.forename: Stuart E
authors.initials: SE
authors.lastname: Turvey
mesh_terms: D000293:Adolescent; D015551:Autoimmunity / Q000235:genetics* / Q000276:immunology; D015618:Histiocytosis, Sinus / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology; D008297:Male; D009154:Mutation / Q000235:genetics* / Q000276:immunology*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D013577:Syndrome
chemical_list: C117307:KRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)