title: Typing TREX1 gene in patients with systemic lupus erythematosus.
abstract: 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 TREX1 gene on chromosome 3. Heterozygous mutations in TREX1 were reported in SLE patients. TREX1 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 TREX1 and neurological manifestations in European SLE patients. Fifty-one SLE patients were screened for TREX1 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%) vs 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 TREX1, which may be pathogenic. The polymorphism of rs11797 was more frequent in SLE patients with neurological manifestations.
authors.affiliation: Rheumatology and Clinical Immunology Unit, Spedali Civili, Brescia; Department of Clinical and Experimental Sciences, University of Brescia; Rheumatology Chair, University of Pavia. elmic83@libero.it.
authors.forename: M
authors.initials: M
authors.lastname: Fredi
authors.forename: M
authors.initials: M
authors.lastname: Bianchi
authors.forename: L
authors.initials: L
authors.lastname: Andreoli
authors.forename: G
authors.initials: G
authors.lastname: Greco
authors.forename: I
authors.initials: I
authors.lastname: Olivieri
authors.forename: S
authors.initials: S
authors.lastname: Orcesi
authors.forename: E
authors.initials: E
authors.lastname: Fazzi
authors.forename: C
authors.initials: C
authors.lastname: Cereda
authors.forename: A
authors.initials: A
authors.lastname: Tincani
mesh_terms: D000483:Alleles; D015415:Biomarkers / Q000097:blood; D005090:Exodeoxyribonucleases / Q000235:genetics*; D060005:Genotyping Techniques / Q000379:methods; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000175:diagnosis / Q000235:genetics*; D020125:Mutation, Missense; D010641:Phenotype; D010750:Phosphoproteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers; D010750:Phosphoproteins; D005090:Exodeoxyribonucleases; C429526:three prime repair exonuclease 1