{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T16:34:04Z","timestamp":1788798844337,"version":"build-2803163510"},"reference-count":31,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,2,15]],"date-time":"2017-02-15T00:00:00Z","timestamp":1487116800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2017,3]]},"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Molecular characterization has shown a wide mutational spectrum underlying haemophilia A (<jats:styled-content style=\"fixed-case\">HA<\/jats:styled-content>) and haemophilia B (<jats:styled-content style=\"fixed-case\">HB<\/jats:styled-content>). Different molecular assays have allowed laboratories to perform genetic testing for F8 and F9 mutations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>Recently, multiplex ligation\u2010dependent probe amplification (<jats:styled-content style=\"fixed-case\">MLPA<\/jats:styled-content>), a simple technique for relative quantitation of targeted genomic regions, has been introduced in <jats:styled-content style=\"fixed-case\">HA<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">HB<\/jats:styled-content> for detection of large deletions and duplications. We want to verify if <jats:styled-content style=\"fixed-case\">MLPA<\/jats:styled-content> might be used at the beginning of the molecular investigation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used it to test 22 patients with suspected large deletions, nine patients negative for mutation detection by other methods and finally, 45 new patients as their first screening test.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Carrier status was also established in 28 related females and gross rearrangements were also searched for by <jats:styled-content style=\"fixed-case\">MLPA<\/jats:styled-content> in 19 females with reduced <jats:styled-content style=\"fixed-case\">FVIII<\/jats:styled-content> or <jats:styled-content style=\"fixed-case\">FIX<\/jats:styled-content> levels. All suspected deletions were confirmed apart from two patients. In patients with a negative screening test, <jats:styled-content style=\"fixed-case\">MLPA<\/jats:styled-content> revealed one large duplication, while in two patients where <jats:styled-content style=\"fixed-case\">MLPA<\/jats:styled-content> was used as the first screening step, an exon duplication was detected. In females with reduced <jats:styled-content style=\"fixed-case\">FVIII<\/jats:styled-content> or <jats:styled-content style=\"fixed-case\">FIX<\/jats:styled-content>, no large deletions or duplications were found.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Owing to its simplicity, <jats:styled-content style=\"fixed-case\">MLPA<\/jats:styled-content> seems useful at the beginning of the molecular investigation, saving all the following steps, where positive. Single exon deletion diagnosis requires caution due to the risk of misdiagnosis, but benefits of <jats:styled-content style=\"fixed-case\">MLPA<\/jats:styled-content> appear to overcome the pitfalls.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hae.13143","type":"journal-article","created":{"date-parts":[[2017,2,16]],"date-time":"2017-02-16T04:42:38Z","timestamp":1487220158000},"source":"Crossref","is-referenced-by-count":8,"title":["Multiplex ligation\u2010dependent probe amplification as first mutation screening for large deletions and duplications in haemophilia"],"prefix":"10.1111","volume":"23","author":[{"given":"D.","family":"Belvini","sequence":"first","affiliation":[{"name":"Transfusion Service Haemophilia Centre and Haematology Castelfranco Veneto Hospital Castelfranco Veneto Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Salviato","sequence":"additional","affiliation":[{"name":"Transfusion Service Haemophilia Centre and Haematology 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