Mutation of DNASE1 in people with systemic lupus erythematosus.
Systemic lupus erythematosus (SLE) is a highly prevalent human autoimmune diseases that causes progressive glomerulonephritis, arthritis and an erythematoid rash. Mice deficient in deoxyribonuclease I (Dnase1) develop an SLE-like syndrome. Here we describe two patients with a heterozygous nonsense mutation in exon 2 of DNASE1, decreased DNASE1 activity and an extremely high immunoglobulin G titer against nucleosomal antigens. These data are consistent with the hypothesis that a direct connection exists between low activity of DNASE1 and progression of human SLE.
Yasutomo
K
K
Department of Pediatrics, School of Medicine, University of Tokushima, Tokushima 770-8503, Japan. yasutomo@clin.med.tokushima-u.ac.jp
Horiuchi
T
T
Kagami
S
S
Tsukamoto
H
H
Hashimura
C
C
Urushihara
M
M
Kuroda
Y
Y
D000293:Adolescent; D000483:Alleles; D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood; D001323:Autoantibodies / Q000097:blood; D001402:B-Lymphocytes / Q000201:enzymology; D004252:DNA Mutational Analysis; D003850:Deoxyribonuclease I / Q000097:blood / Q000235:genetics*; D018450:Disease Progression; D004789:Enzyme Activation / Q000235:genetics; D005260:Female; D006579:Heterozygote; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D051379:Mice; D009154:Mutation; D009707:Nucleosomes / Q000276:immunology; D011110:Polymorphism, Genetic; D012859:Sjogren's Syndrome / Q000097:blood / Q000150:complications / Q000175:diagnosis
D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D007074:Immunoglobulin G; D009707:Nucleosomes; D003850:Deoxyribonuclease I