Mutation of DNASE1 in people with systemic lupus erythematosus

• Published in: Nature genetics Vol. 28; no. 4; pp. 313 - 314
• Main Authors: Yasutomo, Koji, Horiuchi, Takahiko, Kagami, Shoji, Tsukamoto, Hiroshi, Hashimura, Chinami, Urushihara, Maki, Kuroda, Yasuhiro
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 01.08.2001
• Subjects: Adolescent; Alleles; Animals; Antibodies, Antinuclear - blood; Antigens; Autoantibodies - blood; Autoimmune diseases; B-Lymphocytes - enzymology; Biological and medical sciences; Complications and side effects; Deoxyribonuclease I - blood; Deoxyribonuclease I - genetics; Diagnosis; Disease Progression; DNA Mutational Analysis; DNASE1 gene; Enzyme Activation - genetics; Enzymes; Female; Fundamental and applied biological sciences. Psychology; Gene mutations; Genes. Genome; Health aspects; Heterozygote; Humans; Immunoglobulin G - blood; Immunoglobulins; Lupus; Lupus Erythematosus, Systemic - complications; Lupus Erythematosus, Systemic - diagnosis; Lupus Erythematosus, Systemic - genetics; Lymphocytes; Mice; Molecular and cellular biology; Molecular genetics; Mutation; Nucleosomes - immunology; Patients; Polymorphism, Genetic; Publishing; Risk factors; Sjogren's Syndrome - blood; Sjogren's Syndrome - complications; Sjogren's Syndrome - diagnosis; Systemic lupus erythematosus; Tetanus; Tumor necrosis factor-TNF; Japan; Immunopathology; Connective tissue disease; Skin disease; Systemic disease; Autoimmune disease; Lupus erythematosus; Systemic; Mutation
• ISSN: 1061-4036; 1546-1718
• DOI: 10.1038/91070

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.