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- Title
Perforin gene defects in familial hemophagocytic lymphohistiocytosis.
- Authors
Stepp, S E; Dufourcq-Lagelouse, R; Le Deist, F; Bhawan, S; Certain, S; Mathew, P A; Henter, J I; Bennett, M; Fischer, A; de Saint Basile, G; Kumar, V
- Abstract
Familial hemophagocytic lymphohistiocytosis (FHL) is a rare, rapidly fatal, autosomal recessive immune disorder characterized by uncontrolled activation of T cells and macrophages and overproduction of inflammatory cytokines. Linkage analyses indicate that FHL is genetically heterogeneous and linked to 9q21.3-22, 10q21-22, or another as yet undefined locus. Sequencing of the coding regions of the perforin gene of eight unrelated 10q21-22-linked FHL patients revealed homozygous nonsense mutations in four patients and missense mutations in the other four patients. Cultured lymphocytes from patients had defective cytotoxic activity, and immunostaining revealed little or no perforin in the granules. Thus, defects in perforin are responsible for 10q21-22-linked FHL. Perforin-based effector systems are, therefore, involved not only in the lysis of abnormal cells but also in the down-regulation of cellular immune activation.
- Publication
Science (New York, N.Y.), 1999, Vol 286, Issue 5446, p1957
- ISSN
0036-8075
- Publication type
Journal Article
- DOI
10.1126/science.286.5446.1957