Trizzino, A., zur Stadt, U., Ueda, I., Risma, K., Janka, G., Ishii, E., Beutel, K., Sumegi, J., Cannella, S., Pende, D., Mian, A., Henter, J.I., Griffiths, G., Santoro, A., Filipovich, A. and Aricò, M., Histiocyte Society HLH Study Group (2008) Genotype-Phenotype Study of Familial Haemophagocytic Lymphohistiocytosis Due to Perforin Mutations. Journal of Medical Genetics, 45, 15-21.
http://dx.doi.org/10.1136/jmg.2007.052670

has been cited by the following article:

• TITLE: The Cell Biology of Systemic Hyperinflammation Resulting from Failed Cytolytic Target Cell Killing

  AUTHORS: Bor Luen Tang

  KEYWORDS: Cytokine Storms, Cytolytic T Lymphocytes (CTLs), Familial Hemophagocytic Lymphohistiocytosis (FHL), Natural Killer (NK) Cells, Hyperinflammation

  JOURNAL NAME: CellBio, Vol.4 No.3, December 22, 2015

  ABSTRACT: Mutations in genes encoding a key component of cytotoxic granules, or the machinery for their release, underlie the systemic hyperiflammatory symptoms of familial hemophagocytic lymphohistiocytosis (FHL), a typically pediatric onset autosomal recessive disorder with five known genetic subtypes (FHL1 - 5). FHL1 mutations have been mapped to chromosome 9, while the respective genes mutated in FHL2 (PRF1), FHL3 (UNC13D/Munc13-4), FHL4 (STX11) and FHL5 (STXBP2/ Munc18b/Munc18-2) have been identified. Perforin gene mutation directly affected the cytolytic activity of the cytotoxic granules. All the other FHL mutations appear to affect some aspect of cytotoxic granule exocytosis, resulting in impaired target cell killing by cytolytic T lymphocytes (CTLs) and/or natural killer (NK) cells. Recent findings suggest that failure to kill and detach from target cells, and prolonged synapse connection time, promote cytokine hypersecretion by the defective CTLs and NKs, which in turn result in systemic inflammation. Deciphering the genetics of FHL has contributed towards our understanding of the cell biology of hyperinflammatory responses and hemophagocytic lymphohistiocytosis accompanying pathological conditions such as cancer and viral infections.