Type I interferonopathies with novel compound heterozygous TREX1 mutations in two siblings with different symptoms responded to tofacitinib
| Autor: | Tao Wang, Yuyan Yang, Xue Zhang, Yuehua Liu, Yaping Liu, Jiaxing Song, Lu Yang, Huilei Miao, Shiyu Zhang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Proband Male Interferonopathy lcsh:Diseases of the musculoskeletal system Aicardi-Goutières syndrome Compound heterozygosity 0302 clinical medicine Piperidines Immunology and Allergy Medicine Missense mutation Frameshift Mutation Exome sequencing Skin Genetics Sanger sequencing education.field_of_study Familial chilblain lupus lcsh:RJ1-570 Compound heterozygote Pedigree 030220 oncology & carcinogenesis Child Preschool Interferon Type I symbols Female Research Article Heterozygote TREX1 Three prime repair exonuclease 1 Mutation Missense Frameshift mutation Autoimmune Diseases 03 medical and health sciences symbols.namesake Rheumatology Exome Sequencing Humans education Protein Kinase Inhibitors Tofacitinib business.industry Siblings lcsh:Pediatrics Phosphoproteins 030104 developmental biology Exodeoxyribonucleases Pyrimidines Pediatrics Perinatology and Child Health lcsh:RC925-935 business |
| Zdroj: | Pediatric Rheumatology Online Journal, Vol 19, Iss 1, Pp 1-8 (2021) Pediatric Rheumatology Online Journal |
| ISSN: | 1546-0096 |
| Popis: | Background Type I interferonopathies are a group of rare autoimmune diseases characterised by excessive activation of type I interferon that leads to disturbances in immune function. Three prime repair exonuclease 1 (TREX1) is an important exonuclease and plays an important role in DNA damage repair. TREX1 mutations are associated with many type I interferonopathies. Studies have been published on the effectiveness of tofacitinib in the treatment of type I interferonopathies. The aim of this study is to identify the pathogenic variation in a Chinese family with type I interferonopathies and to observe the therapeutic effects of tofacitinib. Methods A Chinese family with two members with type I interferonopathies was investigated. Whole exome sequencing and Sanger sequencing were applied for mutation screening using peripheral blood DNA of the patient and her family members. Sequencing results were analysed using bioinformatics software tools including VarCards and PolyPhen-2. Close clinical follow-up and observation were used to record changes in the disease before and after treatment with tofacitinib. Results Compound heterozygous variants of TREX1 were observed in the patient’s genome. One was a missense variant (NM_016381; c.C227T; p.Ala76Val) from the patient’s father, and the other was a frameshift variant (NM_016381; c.458dupA; p.Gln153Glnfs*3) from the patient’s mother. One of the proband’s elder brothers with similar skin lesions also carried these two variants. This brother of the proband had more serious cutaneous involvement with the comorbidity of cerebral palsy. These TREX1 variants have not been reported in previous studies and are predicted to be highly pathogenic. The proband was given tofacitinib that led to a marked improvement. Conclusions We identified two novel complex heterozygous variants in the TREX1 gene, which may underlie the molecular pathogenesis of the type I interferonopathies observed in members of this family. Tofacitinib could be an alternative treatment for this disease. |
| Databáze: | OpenAIRE |
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