Typing TREX1 gene in patients with systemic lupus erythematosus
An impaired expression of interferon-α regulated genes has been reported in patients with either systemic lupus erythematosus (SLE) or Aicardi-Goutières syndrome (AGS), a rare monogenic encephalopathy with onset in infancy. One of mutations causing AGS is located in the <em>TREX1</em> ge...
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doaj-29daa80755b3402b8680bce2121c892f2020-11-25T01:07:35ZengPAGEPress PublicationsReumatismo0048-74492240-26832015-06-016711710.4081/reumatismo.2015.782674Typing TREX1 gene in patients with systemic lupus erythematosusM. Fredi0M. Bianchi1L. Andreoli2G. Greco3I. Olivieri4S. Orcesi5E. Fazzi6C. Cereda7A. Tincani8Rheumatology and Clinical Immunology Unit, Spedali Civili, Brescia; Department of Clinical and Experimental Sciences, University of Brescia; Rheumatology Chair, University of PaviaLaboratory of Experimental Neurobiology, C. Mondino National Institute of Neurology Foundation, PaviaRheumatology and Clinical Immunology Unit, Spedali Civili, Brescia; Department of Clinical and Experimental Sciences, University of BresciaLaboratory of Experimental Neurobiology, C. Mondino National Institute of Neurology Foundation, PaviaChild Neurology and Psychiatry Unit, C. Mondino National Institute of Neurology Foundation, PaviaChild Neurology and Psychiatry Unit, C. Mondino National Institute of Neurology Foundation, PaviaChild Neurology and Psychiatry Unit, Mother Child Department, Civil Hospital, University of BresciaLaboratory of Experimental Neurobiology, C. Mondino National Institute of Neurology Foundation, PaviaRheumatology and Clinical Immunology Unit, Spedali Civili, Brescia; Department of Clinical and Experimental Sciences, University of BresciaAn impaired expression of interferon-α regulated genes has been reported in patients with either systemic lupus erythematosus (SLE) or Aicardi-Goutières syndrome (AGS), a rare monogenic encephalopathy with onset in infancy. One of mutations causing AGS is located in the <em>TREX1</em> gene on chromosome 3. Heterozygous mutations in <em>TREX1</em> were reported in SLE patients. <em>TREX1</em> is a DNA exonuclease with specificity for ssDNA. An impairment of its activity may result in the accumulation of nucleid acid. A recent study described a significant association between a haplotype including several common single nucleotide polymorphisms (SNPs) of <em>TREX1</em> and neurological manifestations in European SLE patients. Fifty-one SLE patients were screened for <em>TREX1</em> gene, and the corresponding data were collected from clinical charts. A novel heterozygous variant (p.Asp130Asn) was identified in one patient and in none of 150 controls. A missense variation was located in one of the three active sites of the gene and was classified as probably damaging. Variations of SNP rs11797 were detected in 33 SLE patients and a variation of rs3135944 in one. A significantly higher rate of the minor allele (T nucleotide) of SNP rs11797 was found in SLE patients with neuropsychiatric manifestations [12/16 (75%) <em>vs</em> 28/86 (32.5%) O=0.002, odds ratio=6.42 95% confidence interval (1.7-26.2)]. Only 1 out of 8 patients (12.5%) with neuropsychiatric SLE carried the wild-type form in homozygosity. Although we analyzed a small number of patients, we found a novel variation of <em>TREX1</em>, which may be pathogenic. The polymorphism of rs11797 was more frequent in SLE patients with neurological manifestations.http://www.reumatismo.org/index.php/reuma/article/view/782TREX1, Novel variation, Neuropsychiatric systemic lupus erythematosus. |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
M. Fredi M. Bianchi L. Andreoli G. Greco I. Olivieri S. Orcesi E. Fazzi C. Cereda A. Tincani |
spellingShingle |
M. Fredi M. Bianchi L. Andreoli G. Greco I. Olivieri S. Orcesi E. Fazzi C. Cereda A. Tincani Typing TREX1 gene in patients with systemic lupus erythematosus Reumatismo TREX1, Novel variation, Neuropsychiatric systemic lupus erythematosus. |
author_facet |
M. Fredi M. Bianchi L. Andreoli G. Greco I. Olivieri S. Orcesi E. Fazzi C. Cereda A. Tincani |
author_sort |
M. Fredi |
title |
Typing TREX1 gene in patients with systemic lupus erythematosus |
title_short |
Typing TREX1 gene in patients with systemic lupus erythematosus |
title_full |
Typing TREX1 gene in patients with systemic lupus erythematosus |
title_fullStr |
Typing TREX1 gene in patients with systemic lupus erythematosus |
title_full_unstemmed |
Typing TREX1 gene in patients with systemic lupus erythematosus |
title_sort |
typing trex1 gene in patients with systemic lupus erythematosus |
publisher |
PAGEPress Publications |
series |
Reumatismo |
issn |
0048-7449 2240-2683 |
publishDate |
2015-06-01 |
description |
An impaired expression of interferon-α regulated genes has been reported in patients with either systemic lupus erythematosus (SLE) or Aicardi-Goutières syndrome (AGS), a rare monogenic encephalopathy with onset in infancy. One of mutations causing AGS is located in the <em>TREX1</em> gene on chromosome 3. Heterozygous mutations in <em>TREX1</em> were reported in SLE patients. <em>TREX1</em> is a DNA exonuclease with specificity for ssDNA. An impairment of its activity may result in the accumulation of nucleid acid. A recent study described a significant association between a haplotype including several common single nucleotide polymorphisms (SNPs) of <em>TREX1</em> and neurological manifestations in European SLE patients. Fifty-one SLE patients were screened for <em>TREX1</em> gene, and the corresponding data were collected from clinical charts. A novel heterozygous variant (p.Asp130Asn) was identified in one patient and in none of 150 controls. A missense variation was located in one of the three active sites of the gene and was classified as probably damaging. Variations of SNP rs11797 were detected in 33 SLE patients and a variation of rs3135944 in one. A significantly higher rate of the minor allele (T nucleotide) of SNP rs11797 was found in SLE patients with neuropsychiatric manifestations [12/16 (75%) <em>vs</em> 28/86 (32.5%) O=0.002, odds ratio=6.42 95% confidence interval (1.7-26.2)]. Only 1 out of 8 patients (12.5%) with neuropsychiatric SLE carried the wild-type form in homozygosity. Although we analyzed a small number of patients, we found a novel variation of <em>TREX1</em>, which may be pathogenic. The polymorphism of rs11797 was more frequent in SLE patients with neurological manifestations. |
topic |
TREX1, Novel variation, Neuropsychiatric systemic lupus erythematosus. |
url |
http://www.reumatismo.org/index.php/reuma/article/view/782 |
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