PMID- 10583959
OWN - NLM
STAT- MEDLINE
DCOM- 19991216
LR  - 20220316
IS  - 0036-8075 (Print)
IS  - 0036-8075 (Linking)
VI  - 286
IP  - 5446
DP  - 1999 Dec 3
TI  - Perforin gene defects in familial hemophagocytic lymphohistiocytosis.
PG  - 1957-9
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.
FAU - Stepp, S E
AU  - Stepp SE
AD  - Department of Pathology and the Graduate Program in Immunology, University of
      Texas Southwestern Medical School, Dallas, TX 75235, USA.
FAU - Dufourcq-Lagelouse, R
AU  - Dufourcq-Lagelouse R
FAU - Le Deist, F
AU  - Le Deist F
FAU - Bhawan, S
AU  - Bhawan S
FAU - Certain, S
AU  - Certain S
FAU - Mathew, P A
AU  - Mathew PA
FAU - Henter, J I
AU  - Henter JI
FAU - Bennett, M
AU  - Bennett M
FAU - Fischer, A
AU  - Fischer A
FAU - de Saint Basile, G
AU  - de Saint Basile G
FAU - Kumar, V
AU  - Kumar V
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Science
JT  - Science (New York, N.Y.)
JID - 0404511
RN  - 0 (Codon, Terminator)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Pore Forming Cytotoxic Proteins)
RN  - 126465-35-8 (Perforin)
RN  - EC 3.4.21.- (GZMB protein, human)
RN  - EC 3.4.21.- (Granzymes)
RN  - EC 3.4.21.- (Serine Endopeptidases)
SB  - IM
MH  - Antigen-Presenting Cells/immunology
MH  - Cell Death
MH  - Cell Line
MH  - Cells, Cultured
MH  - Chromosome Mapping
MH  - Chromosomes, Human, Pair 10/*genetics
MH  - Codon, Terminator
MH  - Cytoplasmic Granules/chemistry
MH  - Cytotoxicity, Immunologic
MH  - Frameshift Mutation
MH  - Genetic Linkage
MH  - Granzymes
MH  - Heterozygote
MH  - Histiocytosis, Non-Langerhans-Cell/*genetics/immunology
MH  - Humans
MH  - Lymphocyte Activation
MH  - Membrane Glycoproteins/analysis/*genetics/physiology
MH  - Mutation, Missense
MH  - Perforin
MH  - Point Mutation
MH  - Pore Forming Cytotoxic Proteins
MH  - Serine Endopeptidases/analysis
MH  - T-Lymphocytes, Cytotoxic/chemistry/immunology
EDAT- 1999/12/03 00:00
MHDA- 1999/12/03 00:01
CRDT- 1999/12/03 00:00
PHST- 1999/12/03 00:00 [pubmed]
PHST- 1999/12/03 00:01 [medline]
PHST- 1999/12/03 00:00 [entrez]
AID - 8053 [pii]
AID - 10.1126/science.286.5446.1957 [doi]
PST - ppublish
SO  - Science. 1999 Dec 3;286(5446):1957-9. doi: 10.1126/science.286.5446.1957.