{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T01:08:49Z","timestamp":1778720929098,"version":"3.51.4"},"reference-count":44,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2001,12,23]],"date-time":"2001-12-23T00:00:00Z","timestamp":1009065600000},"content-version":"vor","delay-in-days":113,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Scand J Immunol"],"published-print":{"date-parts":[[2001,9]]},"abstract":"<jats:p>Bruton's tyrosine kinase (<jats:italic>Btk<\/jats:italic>) is a nonreceptor tyrosine kinase, critical for B\u2010cell development and function. Mutations that inactivate this kinase were found in families with X\u2010linked agammaglobulinaemia (XLA). In this study the <jats:italic>Btk<\/jats:italic> gene was analyzed in 13 registered Greek patients with XLA phenotype originated from 12 unrelated families, in order to provide a definite diagnosis of the XLA. The structure of Btk was analyzed at the cDNA level using the recently developed method, NIRCA (Non\u2010Isotopic\u2010Rnase\u2010Cleavage\u2010Assay). Alterations were detected in all patients and sequencing analysis confirmed the results and defined six novel XLA\u2010associated <jats:italic>Btk<\/jats:italic> mutations (three missense mutations: C337G, L346R, L452P; one nonsense mutation: Y392X, and two frameshift alterations: c1211\u20131212delA, c1306\u20131307insA). Having defined the genetic alteration in the affected males of these families, the information was used to design polymerase chain reaction (PCR) primers and the <jats:italic>Btk<\/jats:italic> segments containing the mutated sequences were amplified from peripheral blood derived genomic DNA of potential female carriers. The PCR products were directly sequenced and carrier status was determined in 12 out of 16 phenotypically normal females analyzed. This protocol can be used once the nature of the <jats:italic>Btk<\/jats:italic> mutation has been defined in one of the affected males and provides a convenient, simple and reliable way to determine the carrier status of other female family members. Molecular genetic analysis constitutes a determinative tool for the definitive diagnosis of XLA and may allow accurate carrier and prenatal diagnosis for genetic counselling.<\/jats:p>","DOI":"10.1046\/j.1365-3083.2001.00967.x","type":"journal-article","created":{"date-parts":[[2003,3,12]],"date-time":"2003-03-12T20:16:51Z","timestamp":1047500211000},"page":"321-327","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Analysis of <i>Btk<\/i> Mutations in Patients with X\u2010Linked Agammaglobulinaemia (XLA) and Determination of Carrier Status in\u00a0Normal Female Relatives: a Nationwide Study of <i>Btk<\/i> Deficiency in\u00a0Greece"],"prefix":"10.1111","volume":"54","author":[{"given":"M.","family":"Speletas","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Kanariou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F.","family":"Kanakoudi\u2010Tsakalidou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E.","family":"Papadopoulou\u2010Alataki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K.","family":"Arvanitidis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E.","family":"Pardali","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Constantopoulos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G.","family":"Kartalis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Vihinen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P.","family":"Sideras","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K.","family":"Ritis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2001,12,23]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2776(08)60631-8"},{"key":"e_1_2_6_3_2","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1093\/hmg\/3.suppl_1.1457","article-title":"Molecular 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