title: Late-onset cases of familial hemophagocytic lymphohistiocytosis with missense perforin gene mutations.
abstract: Since the discovery of perforin gene mutations in familial hemophagocytic lymphohistiocytosis (FHL) type 2, heterogeneous features in FHL2 patients have been identified in a report of Feldmann et al. as the beginning. This study was conducted to determine the impact of characteristic gene mutations on late-onset (age > or = 7 years) hemophagocytic lymphohistiocytosis episodes. We analyzed perforin gene mutations in three late-onset cases from our registry in Japan and an additional 10 cases from the literature. Of the 13 cases with onset ages of a median of 10 (range 7-49) years, nine had homozygous and four had compound heterozygous missense mutations of the perforin gene. None had homozygous nonsense mutations. Our data suggest that nonsense perforin gene mutations yield early onset and missense mutations late onset in FHL2 cases.
authors.affiliation: Department of Pediatrics, Kyoto Prefectural University of Medicine, Kyoto, Japan. u194@koto.kpu-m.ac.jp
authors.forename: Ikuyo
authors.initials: I
authors.lastname: Ueda
authors.forename: Yumi
authors.initials: Y
authors.lastname: Kurokawa
authors.forename: Kenichi
authors.initials: K
authors.lastname: Koike
authors.forename: Shuichi
authors.initials: S
authors.lastname: Ito
authors.forename: Akifumi
authors.initials: A
authors.lastname: Sakata
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Matsumora
authors.forename: Takashi
authors.initials: T
authors.lastname: Fukushima
authors.forename: Akira
authors.initials: A
authors.lastname: Morimoto
authors.forename: Eiichi
authors.initials: E
authors.lastname: Ishii
authors.forename: Shinsaku
authors.initials: S
authors.lastname: Imashuku
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002648:Child; D005260:Female; D006801:Humans; D007564:Japan / Q000453:epidemiology; D007694:Killer Cells, Natural / Q000276:immunology; D051359:Lymphohistiocytosis, Hemophagocytic / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010375:Pedigree; D054353:Perforin / Q000235:genetics*
chemical_list: D054353:Perforin