Mutation of DNASE1 in people with systemic lupus erythematosus

  title={Mutation of DNASE1 in people with systemic lupus erythematosus},
  author={Koji Yasutomo and Takahiko Horiuchi and Shoji Kagami and Hiroshi Tsukamoto and Chinami Hashimura and Maki Urushihara and Yasuhiro Kuroda},
  journal={Nature Genetics},
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… 

Study of DNASE I gene polymorphisms in systemic lupus erythematosus susceptibility

Two Spanish patients with SLE with different mutations in the DNASE I gene and very low serum DNase I activity are described, and these mutations are very rare and do not explain the low DNaseI activity found in most patients withSLE.

Loss-of-function variant in DNASE1L3 causes a familial form of systemic lupus erythematosus

A rare autosomal recessive form of SLE is identified, in which autozygome analysis revealed a null mutation in the DNASE1L3 gene, which confirms the critical role of impaired clearance of degraded DNA in SLE pathogenesis.

Dnase1‐deficient mice spontaneously develop a systemic lupus erythematosus‐like disease

A report showed that Dnase1‐deficient mice develop an SLE‐like disease, but these mice also carry a deletion of the gene adjacent to DNase1, which encodes the chaperone TRAP1/HSP75.

DNASE1 and Systemic Lupus Erythematosus

Researchers have long suspected a strong genetic predisposition to the development of systemic lupus erythematosus (SLE). Most genes identified as having a role in SLE, however, have been associated

DNase 1 and systemic lupus erythematosus.

Monogenic Lupus: A Developing Paradigm of Disease

A significant number of genes have been implicated in monogenic lupus, providing valuable insights into a very complex disease process, and the pathogenic mechanisms involved upon inducing autoimmunity are summarized.

Lupus genes at the interface of tolerance and autoimmunity

The genetics of SLE is reviewed in the context of a breach of immune tolerance to conclude that SLE develops, in part, as a consequence of a generalized loss of immuneolerance.



Features of systemic lupus erythematosus in Dnase1-deficient mice

It is found that lack or reduction of Dnase1 is a critical factor in the initiation of human SLE, and in agreement with earlier reports, activities in serum are found to be lower in SLE patients than in normal subjects.

Etiopathogenesis of systemic lupus erythematosus.

Homozygous C1q deficiency causes glomerulonephritis associated with multiple apoptotic bodies

The hypothesis that C1q deficiency causes autoimmunity by impairment of the clearance of apoptotic cells is compatible with the hypothesis that a physiological action of the early part of the classical pathway protects against the development of SLE.

Genetic Studies of Human Lupus in Families

  • F. Arnett
  • Biology, Medicine
    International reviews of immunology
  • 2000
Family studies and recent genome-wide scans in lupus and other autoimmune diseases support the likelihood that some susceptibility loci, as yet unidentified, predispose to several or many autoimmune diseases.

Genetic susceptibility to systemic lupus erythematosus.

Since the genes that predispose to autoimmunity are probably related to key events in pathogenesis, their identification in patients and murine models will almost certainly provide important insight into the breakdown of immunological self-tolerance and the cause of autoimmune disease.

Circulating plasma levels of nucleosomes in patients with systemic lupus erythematosus: correlation with serum antinucleosome antibody titers and absence of clear association with disease activity.

Nucleosome plasma levels may be normal or increased in SLE, and found in patients with active or inactive SLE; longitudinal studies are needed to further establish whether high levels of circulating nucleosomes may predict the occurrence of an SLE flare.

Lupus Susceptibility Genes on Human Chromosome 1

  • B. Tsao
  • Biology
    International reviews of immunology
  • 2000
This review highlights the genetic loci located on chromosome 1 that have recently been associated with SLE, including loci encoding the tumor necrosis factor receptor 2 (TNFR2), complement component Clq, Fc7 receptors, T cell receptor ζ chain, interleukin-10 (IL-10), poly (ADP-ribose) polymerase (PARP), and HRES-1.

Single-nucleotide polymorphisms of T cell receptor ζ chain in patients with systemic lupus erythematosus

The uncommon and equal occurrence of novel single-nucleotide polymorphisms in both SLE patients and normal subjects makes it improbable that they play important roles in genetic susceptibility to SLE.

Apoptosis in lupus SLE-N IV and non-lupus mesangiocapillary glomerulonephritis type I MCGN. I. A comparative study.

The low number of apoptotic cells in renal tissue from patients with SLE-N IV suggests regulation of apoptosis may be altered in the mechanisms of glomerular and tubulointerstitial damage in lupus nephritis, although the reduced apoptosis might simply be due to smaller numbers of cells in fibrotic areas.