{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T19:15:44Z","timestamp":1793646944277,"version":"4.5.1"},"reference-count":19,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T00:00:00Z","timestamp":1762300800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T00:00:00Z","timestamp":1762300800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100002957","name":"Technische Universit\u00e4t Dresden","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002957","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pediatr Rheumatol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Autosomal recessive Aicardi-Gouti\u00e8res syndrome (AGS) and autosomal dominant familial chilblain lupus (FCL) are rare type I interferonopathies that can both result from loss-of-function variants in the\n                      <jats:italic>TREX1<\/jats:italic>\n                      gene, which encodes a DNA exonuclease. Although phenotypic variability is well recognized in\n                      <jats:italic>TREX1<\/jats:italic>\n                      -related disorders, intrafamilial phenotypic discordance is seldom seen.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>\n                      We describe two siblings carrying a novel homozygous\n                      <jats:italic>TREX1<\/jats:italic>\n                      variant (c.341G\u2009&gt;\u2009T, p.Arg114Leu) who exhibit strikingly different clinical phenotypes. The younger sibling presented at 4 months of age with features of AGS, including tetraspasticity, muscular hypotonia and global developmental delay. Brain MRI showed brain atrophy and white matter abnormalities. In contrast, his older brother developed cutaneous chilblain lesions during the cold season at age 3 but was otherwise normally developed. Despite these divergent clinical presentations, both children demonstrated a highly elevated interferon signature.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      This case report expands the genetic and clinical spectrum of\n                      <jats:italic>TREX1<\/jats:italic>\n                      -related disorders and illustrates the considerable phenotypic variability associated with biallelic\n                      <jats:italic>TREX1<\/jats:italic>\n                      variants in AGS. It highlights the complexity of genotype-phenotype correlations in type I interferonopathies and underscores the need for further research into factors that modulate disease expression.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12969-025-01168-2","type":"journal-article","created":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T14:34:21Z","timestamp":1762353261000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Discordant phenotype caused by TREX1 variant in siblings with Aicardi-Gouti\u00e8res syndrome"],"prefix":"10.1186","volume":"23","author":[{"given":"Rou","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Kretschmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulina","family":"Switala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Attia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min Ae","family":"Lee-Kirsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Wolf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,5]]},"reference":[{"issue":"1","key":"1168_CR1","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1002\/ana.410150109","volume":"15","author":"J Aicardi","year":"1984","unstructured":"Aicardi J, Gouti\u00e8res F. A progressive Familial encephalopathy in infancy with calcifications of the basal ganglia and chronic cerebrospinal fluid lymphocytosis. Ann Neurol. 1984;15(1):49\u201354.","journal-title":"Ann Neurol"},{"issue":"1","key":"1168_CR2","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1146\/annurev-med-050715-104506","volume":"68","author":"MA Lee-Kirsch","year":"2017","unstructured":"Lee-Kirsch MA. The type I interferonopathies. Annu Rev Med. 2017;68(1):297\u2013315.","journal-title":"Annu Rev Med"},{"key":"1168_CR3","doi-asserted-by":"crossref","unstructured":"Crow YJ, Chase DS, Schmidt L J, Szynkiewicz M, F GMA, G HL, et al. Characterization of human disease phenotypes associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR, and IFIH1. 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