{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T15:29:38Z","timestamp":1784302178625,"version":"3.55.0"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2022,5,11]],"date-time":"2022-05-11T00:00:00Z","timestamp":1652227200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32141004"],"award-info":[{"award-number":["32141004"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82170739"],"award-info":[{"award-number":["82170739"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Jiangsu Biobank of Clinical Resources","award":["BM2015004-1"],"award-info":[{"award-number":["BM2015004-1"]}]},{"name":"Jiangsu Biobank of Clinical Resources","award":["JSRB2021-02"],"award-info":[{"award-number":["JSRB2021-02"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,10,28]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Heterozygous loss-of-function mutations in the tumour necrosis factor alpha induced protein 3 (TNFAIP3) gene cause an early-onset auto-inflammatory disease named haploinsufficiency of A20 (HA20). Here we describe three unrelated patients with autoimmune lupus nephritis (LN) phenotypes carrying three novel mutations in the TNFAIP3 gene.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Whole-exome sequencing (WES) was used to identify the causative mutations in three biopsy-proven LN patients. Sanger sequencing and quantitative polymerase chain reaction (qPCR) were used to validate the mutations identified by WES. RNA sequencing, qPCR and cytometric bead array was used to detect inflammatory signatures in the patients.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The patients predominantly presented with an autoimmune phenotype, including autoimmune haemolytic anaemia, multipositive autoantibodies and LN. Additionally, novel phenotypes of allergy and pericardial effusion were first reported. WES identified three novel heterozygous mutations in the TNFAIP3 gene, including a novel splicing mutation located in the canonical splicing site (c.634+2T&amp;gt;C)\u00a0resulting in an intron 4 insertion containing a premature stop codon, a de novo novel copy number variation (exon 7\u20138 deletion) and a novel nonsense mutation c.1300_1301delinsTA causing a premature stop codon. We further identified hyperactivation signatures of nuclear factor- kappa B and type I IFN signalling and overproduction of pro-inflammatory cytokines in the blood. This report expanded the phenotype to a later age, as two girls were diagnosed at age 3 years and one man at age 29 years.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Kidney involvement may be the main feature of the clinical spectrum of HA20, even in adults. Genetic screening should be considered for early-onset LN patients.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ckj\/sfac130","type":"journal-article","created":{"date-parts":[[2022,5,5]],"date-time":"2022-05-05T11:18:04Z","timestamp":1651749484000},"page":"2027-2038","source":"Crossref","is-referenced-by-count":28,"title":["Novel loss-of-function mutations in <i>TNFAIP3<\/i> gene in patients with lupus nephritis"],"prefix":"10.1093","volume":"15","author":[{"given":"Changming","family":"Zhang","sequence":"first","affiliation":[{"name":"Kidney Diseases Laboratory, Zhejiang University School of Medicine , Hangzhou, China"},{"name":"National Clinical Research Center of Kidney Diseases, Jinling Hospital , Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Han","sequence":"additional","affiliation":[{"name":"Life Sciences Institute, Zhejiang University , Hangzhou, China"},{"name":"Liangzhu Laboratory, Zhejiang University Medical Center 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