title: Fatal hemophagocytic lymphohistiocytosis in X-linked chronic granulomatous disease associated with a perforin gene variant.
abstract: A patient with previously unrecognized X-linked chronic granulomatous disease (X-CGD) died of multi-organ failure, secondary to ongoing infection and hemophagocytic lymphohistiocytosis (HLH). Post mortem histological investigations were compatible with X-CGD, and a CYBB gene mutation was confirmed. No homozygous mutations in the genes encoding perforin (PRF1), MUNC 13-4 or syntaxin-11 (STX11) were found; however, there was a heterozygous alteration c.1471G>A in the PRF1 gene causing a p.Asp491Asn substitution. Although this substitution has not been reported to cause primary or secondary HLH, we speculate that it may have made the patient more susceptible for HLH under the circumstances of ongoing infection associated with X-CGD.
authors.affiliation: Department of Pediatric Immunology, Wilhelmina Children's Hospital/University Medical Centre Utrecht, Utrecht, The Netherlands. j.vanmontfrans@umcutrecht.nl
authors.forename: Joris M
authors.initials: JM
authors.lastname: van Montfrans
authors.forename: Eva
authors.initials: E
authors.lastname: Rudd
authors.forename: Lisette
authors.initials: L
authors.lastname: van de Corput
authors.forename: Jan-Inge
authors.initials: JI
authors.lastname: Henter
authors.forename: Peter
authors.initials: P
authors.lastname: Nikkels
authors.forename: Nico
authors.initials: N
authors.lastname: Wulffraat
authors.forename: Jaap J
authors.initials: JJ
authors.lastname: Boelens
mesh_terms: D002675:Child, Preschool; D017809:Fatal Outcome; D005260:Female; D006105:Granulomatous Disease, Chronic / Q000150:complications* / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D051359:Lymphohistiocytosis, Hemophagocytic / Q000150:complications* / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000235:genetics; D010375:Pedigree; D054353:Perforin; D011110:Polymorphism, Genetic; D052899:Pore Forming Cytotoxic Proteins / Q000235:genetics*
chemical_list: D008562:Membrane Glycoproteins; C510468:PRF1 protein, human; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases