{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T17:28:23Z","timestamp":1767979703550,"version":"3.49.0"},"reference-count":21,"publisher":"Termedia Sp. z.o.o.","issue":"2","license":[{"start":{"date-parts":[[2022,7,15]],"date-time":"2022-07-15T00:00:00Z","timestamp":1657843200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"},{"start":{"date-parts":[[2022,7,15]],"date-time":"2022-07-15T00:00:00Z","timestamp":1657843200000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"},{"start":{"date-parts":[[2022,7,15]],"date-time":"2022-07-15T00:00:00Z","timestamp":1657843200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cent Eur J Immunol"],"abstract":"<jats:p>Autoimmune lymphoproliferative syndrome (ALPS) is a chronic non-malignant lymphoproliferative disorder caused by mutations in the genes involved in programmed cell death. It is inherited as an autosomal dominant pattern with variable penetrance. In this paper we present the first report of a Macedonian family with ALPS, caused by a novel heterozygous variant in the FAS gene. The next generation sequencing (NGS) analysis in a patient with splenomegaly, suspected for hereditary spherocytosis, showed presence of the FAS c.913dupA, p.Thr305AsnfsTer16 variant. The same variant was present in the patient\u2019s mother, but not in the mother\u2019s parents (proband\u2019s grandparents). Thus, the pathogenic FAS variant has arisen as a de novo event in the proband\u2019s mother. Later, analysis of the newborn affected sister showed presence of the same FAS variant. Additional clinical and laboratory investigations in the proband and her sister confirmed the presence of specific biomarkers for ALPS. A first-line NGS analysis allows identification of the genetic defect and initiation of appropriate clinical examinations to promptly establish the clinical diagnosis in patients with rare diseases. Reverse phenotyping in our case provided a prompt and accurate diagnosis and early initiation of specific therapy.<\/jats:p>","DOI":"10.5114\/ceji.2022.118079","type":"journal-article","created":{"date-parts":[[2022,7,15]],"date-time":"2022-07-15T09:37:43Z","timestamp":1657877863000},"page":"179-182","source":"Crossref","is-referenced-by-count":0,"title":["Autoimmune lymphoproliferative syndrome identified through reverse phenotyping"],"prefix":"10.5114","volume":"47","author":[{"given":"Svetlana","family":"Kocheva","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marija","family":"Gjorgijevska","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marija","family":"Vujovic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kata","family":"Martinova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zorica","family":"Antevska-Trajkova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aleksandra","family":"Jovanovska","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katarina","family":"Stavrikj","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dijana","family":"Plaseska-Karanfilska","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"3061","published-online":{"date-parts":[[2022,7,15]]},"reference":[{"key":"ref-1538746","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1172\/JCI115867","article-title":"A novel lymphoproliferative\/autoimmune syndrome resembling murine lpr\/gld disease","volume":"90","author":"Sneller MC","year":"1992","unstructured":"Sneller MC, Straus SE, Jaffe ES, et al. 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