TY - JOUR
T1 - Perforin gene defects in familial hemophagocytic lymphohistiocytosis
AU - Stepp, Susan E.
AU - Dufourcq-Lagelouse, Rémi
AU - Le Deist, Françoise
AU - Bhawan, Sadhna
AU - Certain, Stéphanie
AU - Mathew, Porunelloor A.
AU - Henter, Jan Inge
AU - Bennett, Michael
AU - Fischer, Alain
AU - De Saint Basile, Geneviève
AU - Kumar, Vinay
PY - 1999/12/3
Y1 - 1999/12/3
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0033520970&partnerID=8YFLogxK
U2 - 10.1126/science.286.5446.1957
DO - 10.1126/science.286.5446.1957
M3 - Article
C2 - 25980028
AN - SCOPUS:0033520970
SN - 0036-8075
VL - 286
SP - 1957
EP - 1959
JO - Science
JF - Science
IS - 5446
ER -