Characteristic perforin gene mutations of haemophagocytic lymphohistiocytosis patients in Japan.
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.
Ueda
Ikuyo
I
Department of Paediatrics, and Department of Clinical Laboratory and Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan. u194@koto.kpu-m.ac.jp
Morimoto
Akira
A
Inaba
Tohru
T
Yagi
Tomohito
T
Hibi
Shigeyoshi
S
Sugimoto
Tohru
T
Sako
Masahiro
M
Yanai
Fumio
F
Fukushima
Takashi
T
Nakayama
Masahiko
M
Ishii
Eiichi
E
Imashuku
Shinsaku
S
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
D018389:Codon, Nonsense; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin