Identification of novel MUNC13-4 mutations in familial haemophagocytic lymphohistiocytosis and functional analysis of MUNC13-4-deficient cytotoxic T lymphocytes

K. Yamamoto, Eiichi Ishii, M. Sako, S. Ohga, K. Furuno, N. Suzuki, I. Ueda, M. Imayoshi, S. Yamamoto, A. Morimoto, H. Takada, T. Hara, S. Imashuku, T. Sasazuki, M. Yasukawa

研究成果: ジャーナルへの寄稿記事

45 引用 (Scopus)


Background: Familial haemophagocytic lymphohistiocytosis (FHL) has an autosomal recessive mode of inheritance and consists of at least three subtypes. FHL2 subtype with perforin (PRF1) mutation accounts for 30% of all FHL cases, while FHL with MUNC13-4 mutation was recently identified and designated as FHL3 subtype. Objective: To examine MUNC13-4 mutations and the cytotoxic function of MUNC13-4 deficient T lymphocytes in Japanese FHL patients Methods: Mutations of MUNC13-4 and the cytotoxicity of MUNC13-4-deficient cytotoxic T lymphocytes (CTL) were analysed in 16 Japanese families with non-FHL2 subtype. Results: Five new mutations of the MUNC13-4 gene were identified in six families. The mutations were in the introns 4, 9, and 18, and exons 8 and 19. Two families had homozygous mutations, while the remaining four had compound heterozygous mutations. Cytotoxicity of MUNC13-4 deficient CTL was low compared with control CTL, but was still present. Clinically, the onset of disease tended to occur late; moreover, natural killer cell activity was not deficient in some FHL3 patients. Conclusions: MUNC13-4 mutations play a role in the development of FHL3 through a defective cytotoxic pathway.

ジャーナルJournal of medical genetics
出版物ステータス出版済み - 10 1 2004


All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)