title: Characteristic perforin gene mutations of haemophagocytic lymphohistiocytosis patients in Japan.
abstract: Perforin gene (PRF1) mutations appear to occur in about 30% of patients with haemophagocytic lymphohistiocytosis (HLH). We tested perforin expression and gene mutations in 14 HLH patients and six patients with Epstein-Barr virus-associated HLH (EBV-HLH) in Japan. Five of the 14 HLH patients had perforin abnormalities. The presence of PRF1 genetic abnormality correlated well with the lack of perforin expression as determined by flow cytometry. Sequencing showed that four patients had a compound heterozygous mutation while the fifth patient had a homozygous mutation. Three of the mutations we detected were novel. In contrast, none of the six EBV-HLH patients showed perforin abnormalities. Our data, combined with the PRF1 mutations in three previously reported Japanese patients, suggest that the 1090-1091delCT and 207delC mutations of the perforin gene are frequently present in Japanese HLH patients (62.5% and 37.5% respectively). Examination of the geographical origins of the ancestors in the perforin-mutant HLH patients revealed that they mostly came from the Western part of Japan, suggesting that the present-day cases may largely derive from a common ancestor.
authors.affiliation: Department of Paediatrics, and Department of Clinical Laboratory and Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan. u194@koto.kpu-m.ac.jp
authors.forename: Ikuyo
authors.initials: I
authors.lastname: Ueda
authors.forename: Akira
authors.initials: A
authors.lastname: Morimoto
authors.forename: Tohru
authors.initials: T
authors.lastname: Inaba
authors.forename: Tomohito
authors.initials: T
authors.lastname: Yagi
authors.forename: Shigeyoshi
authors.initials: S
authors.lastname: Hibi
authors.forename: Tohru
authors.initials: T
authors.lastname: Sugimoto
authors.forename: Masahiro
authors.initials: M
authors.lastname: Sako
authors.forename: Fumio
authors.initials: F
authors.lastname: Yanai
authors.forename: Takashi
authors.initials: T
authors.lastname: Fukushima
authors.forename: Masahiko
authors.initials: M
authors.lastname: Nakayama
authors.forename: Eiichi
authors.initials: E
authors.lastname: Ishii
authors.forename: Shinsaku
authors.initials: S
authors.lastname: Imashuku
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D018389:Codon, Nonsense; D020031:Epstein-Barr Virus Infections / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006579:Heterozygote; D015616:Histiocytosis, Non-Langerhans-Cell / Q000235:genetics* / Q000821:virology; D006720:Homozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007564:Japan; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D010375:Pedigree; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins
chemical_list: D018389:Codon, Nonsense; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin