title: Fas ligand mutation in a patient with systemic lupus erythematosus and lymphoproliferative disease.
abstract: The pathogenesis of systemic lupus erythematosus (SLE) is multifactorial and multigenetic. The apoptosis genes, fas and fas ligand (fasL), are candidate contributory genes in human SLE, as mutations of these genes result in autoimmunity in several murine models of this disease. In humans, fas mutations result in a familial autoimmune lymphoproliferative syndrome, but defects in FasL have not yet been identified. In this study, DNA from 75 patients with SLE was screened by single-stranded conformational polymorphism analysis for potential mutations of the extracellular domain of FasL. A heterozygous single-stranded conformational polymorphism for FasL, was identified in one SLE patient, who exhibited lymphadenopathy. Molecular cloning and sequencing indicated that the genomic DNA of this patient contained an 84-bp deletion within exon 4 of the fasL gene, resulting in a predicted 28 amino acid in-frame deletion. Analysis of PBMC from this patient revealed decreased FasL activity, decreased activation-induced cell death, and increased T cell proliferation after activation. This is the first report of defective FasL-mediated apoptosis related to a mutation of the human Fasl, gene in a patient with SLE and suggests that fasL mutations are an uncommon cause of the disease.
authors.affiliation: Department of Medicine, The University of Alabama at Birmingham 35294, USA.
authors.forename: J
authors.initials: J
authors.lastname: Wu
authors.forename: J
authors.initials: J
authors.lastname: Wilson
authors.forename: J
authors.initials: J
authors.lastname: He
authors.forename: L
authors.initials: L
authors.lastname: Xiang
authors.forename: P H
authors.initials: PH
authors.lastname: Schur
authors.forename: J D
authors.initials: JD
authors.lastname: Mountz
mesh_terms: D000595:Amino Acid Sequence; D017209:Apoptosis / Q000235:genetics; D001483:Base Sequence; D044383:Black People / Q000235:genetics; D053222:Fas Ligand Protein; D005820:Genetic Testing; D006579:Heterozygote; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008232:Lymphoproliferative Disorders / Q000235:genetics*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D018807:Polymorphism, Single-Stranded Conformational; D017384:Sequence Deletion; D013577:Syndrome; D044465:White People / Q000235:genetics
chemical_list: C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins