{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T20:38:59Z","timestamp":1772915939844,"version":"3.50.1"},"reference-count":15,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2006,3,1]],"date-time":"2006-03-01T00:00:00Z","timestamp":1141171200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int J Immunogenetics"],"published-print":{"date-parts":[[2006,4]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Familial haemophagocytic lymphohistiocytosis (FHLH) is a heterogeneous autosomal recessive disorder characterized by hyperactivation of monocytes\/macrophages. Perforin (<jats:italic>PRF1<\/jats:italic>) gene alterations have been documented in 40% of patients with FHLH. Although several mutations have been identified, a clear correlation between the individual molecular alteration and the phenotypic expression of the disease is still unclear. In particular, the role that the A91V substitution plays in the pathogenesis of the disease is still controversial. In the effort to make a conclusive remark to this issue, we here report on the frequency of the A91V mutation in a group of unrelated healthy families obtained from the \u2018Centre d\u2019Etude du Polymorphisme Humain\u2019 (CEPH), which are considered representative of the worldwide population. This frequency was compared to that observed in FHLH patients recruited through the Italian National Registry. The frequency in CEPH healthy subjects is 3.7%, thus indicating that the alteration represents a polymorphism. However, the frequency of this alteration in FHLH patients associated with <jats:italic>PRF1<\/jats:italic> mutation is much higher than that observed in controls (26.2%, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.0002), suggesting that the alteration is an important genetic susceptibility factor.<\/jats:p>","DOI":"10.1111\/j.1744-313x.2006.00582.x","type":"journal-article","created":{"date-parts":[[2006,3,1]],"date-time":"2006-03-01T11:24:18Z","timestamp":1141212258000},"page":"123-125","source":"Crossref","is-referenced-by-count":26,"title":["A91V perforin variation in healthy subjects and FHLH patients"],"prefix":"10.1111","volume":"33","author":[{"given":"R.","family":"Busiello","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G.","family":"Fimiani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. G.","family":"Miano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Aric\u00f2","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Santoro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. V.","family":"Ursini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.","family":"Pignata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,3]]},"reference":[{"key":"e_1_2_5_2_1","first-page":"197","article-title":"Hemophagocytic lymphohistiocytosis. Report of 122 children from the International Registry. FHL Study Group of the Histiocyte Society","volume":"10","author":"Aric\u00f2 M.","year":"1996","journal-title":"Leukemia"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-10-3551"},{"key":"e_1_2_5_4_1","first-page":"1909","article-title":"Role of A91V mutation in perforin gene in haemophagocytic lymphohistiocytosis","volume":"104","author":"Busiello R.","year":"2004","journal-title":"Blood"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-04-1030"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.38.9.643"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0888-7543(90)90491-C"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1086\/318796"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.2002.03534.x"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2003.011528"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-02-0733"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.286.5446.1957"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.2002.03266.x"},{"key":"e_1_2_5_14_1","doi-asserted-by":"crossref","unstructured":"Trambas C. Gallo F. Pende D. Marcenaro S. Moretta L. De Fusco C. Notarangelo L. Arico M.&Griffiths G.(2005)A single amino acid change A91V lead to conformational changes which can impair processing to the active form of perforin.Blood 106 932\u20137.","DOI":"10.1182\/blood-2004-09-3713"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.2003.04298.x"},{"key":"e_1_2_5_16_1","doi-asserted-by":"crossref","unstructured":"Voskoboinik I. Thia M.C.&Trapani J.A.(2005)A functional analysis of the putative polymorphisms A91V and N252S and 22 missense perforin mutations associated with hemophagocytic lymphohistiocytosis.Blood 105 4700\u20136.","DOI":"10.1182\/blood-2004-12-4935"}],"container-title":["International Journal of Immunogenetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1744-313X.2006.00582.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1744-313X.2006.00582.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,10]],"date-time":"2023-10-10T23:49:07Z","timestamp":1696981747000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1744-313X.2006.00582.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,3]]},"references-count":15,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2006,4]]}},"alternative-id":["10.1111\/j.1744-313X.2006.00582.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1744-313x.2006.00582.x","archive":["Portico"],"relation":{},"ISSN":["1744-3121","1744-313X"],"issn-type":[{"value":"1744-3121","type":"print"},{"value":"1744-313X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,3]]}}}