{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:29:22Z","timestamp":1777508962512,"version":"3.51.4"},"reference-count":27,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2014,4,8]],"date-time":"2014-04-08T00:00:00Z","timestamp":1396915200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001409","name":"Department of Science and Technology, Ministry of Science and Technology","doi-asserted-by":"publisher","award":["SP\/SO\/B-52\/2001"],"award-info":[{"award-number":["SP\/SO\/B-52\/2001"]}],"id":[{"id":"10.13039\/501100001409","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Prof. Gunther Landbeck fellowship","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2014,7]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Linkage analysis in autosomal inherited von Willebrand disease (<jats:styled-content style=\"fixed-case\">VWD<\/jats:styled-content>) is important to diagnose the carriers and reduce the burden of severe type <jats:styled-content style=\"fixed-case\">VWD<\/jats:styled-content>. The study was designed to identify the carriers and estimate the frequency of variable number of tandem repeats (<jats:styled-content style=\"fixed-case\">VNTR<\/jats:styled-content>) instability in <jats:styled-content style=\"fixed-case\">VWD<\/jats:styled-content> families. Carrier detection was performed in eight recessive type 3 <jats:styled-content style=\"fixed-case\">VWD<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">VWD<\/jats:styled-content>3) families using <jats:styled-content style=\"fixed-case\">VNTR<\/jats:styled-content>s VWF1 and <jats:styled-content style=\"fixed-case\">VWF<\/jats:styled-content>2, <jats:italic>Rsa<\/jats:italic>I (789Thr\/Ala) linkage markers, multimer analysis and <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> sequencing. Moreover, five dominant <jats:styled-content style=\"fixed-case\">VWD<\/jats:styled-content> families were studied through <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> sequencing and multimer analysis. Frequency of <jats:italic><jats:styled-content style=\"fixed-case\">VWF<\/jats:styled-content><\/jats:italic> <jats:styled-content style=\"fixed-case\">VNTR<\/jats:styled-content> instability was investigated in 20 <jats:styled-content style=\"fixed-case\">VWD<\/jats:styled-content> families. In <jats:styled-content style=\"fixed-case\">VWD<\/jats:styled-content>3 families, a total of 22 (81.5%) carriers were identified using <jats:styled-content style=\"fixed-case\">VWF<\/jats:styled-content>1 and <jats:styled-content style=\"fixed-case\">VWF<\/jats:styled-content>2 markers. However, only 13(48.1%) carriers were identified through <jats:italic>Rsa<\/jats:italic>I markers. Mutation screening revealed 22(81.5%) carriers in <jats:styled-content style=\"fixed-case\">VWD<\/jats:styled-content>3 and 4 (33.3%) carriers in <jats:styled-content style=\"fixed-case\">VWD<\/jats:styled-content>2 families. In comparison to <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> sequencing, the accuracy of <jats:styled-content style=\"fixed-case\">VWF<\/jats:styled-content>1 and <jats:styled-content style=\"fixed-case\">VWF<\/jats:styled-content>2 markers in <jats:styled-content style=\"fixed-case\">VWD<\/jats:styled-content>3 was 85.7% while <jats:italic>Rsa<\/jats:italic>I could identify 68.2% carriers accurately. Mutations p.R1205H and p.C1272R were identified as <jats:italic>de novo<\/jats:italic> in families. Multimer analysis confirmed the identified carriers in <jats:styled-content style=\"fixed-case\">VWD<\/jats:styled-content>2 families. Three <jats:styled-content style=\"fixed-case\">VWD<\/jats:styled-content> families were found to be carrying <jats:styled-content style=\"fixed-case\">VNTR<\/jats:styled-content> instability for <jats:styled-content style=\"fixed-case\">VWF<\/jats:styled-content>1 and <jats:styled-content style=\"fixed-case\">VWF<\/jats:styled-content>2 locus. <jats:styled-content style=\"fixed-case\">VNTR<\/jats:styled-content>s could be an effective linkage markers for carrier detection in <jats:styled-content style=\"fixed-case\">VWD<\/jats:styled-content>3 families. However, in the event of germline <jats:italic>de novo<\/jats:italic> mutations and <jats:styled-content style=\"fixed-case\">VNTR<\/jats:styled-content> instability, it may confound risk of misdiagnosis of carriers. Multimer analysis could be an alternative way of carrier detection in dominant type 2A and type 2B <jats:styled-content style=\"fixed-case\">VWD<\/jats:styled-content> families.<\/jats:p>","DOI":"10.1111\/hae.12441","type":"journal-article","created":{"date-parts":[[2014,4,8]],"date-time":"2014-04-08T10:45:20Z","timestamp":1396953920000},"source":"Crossref","is-referenced-by-count":3,"title":["Germline <i>de novo<\/i> mutations and linkage markers vs. DNA sequencing for carrier detection in von Willebrand disease"],"prefix":"10.1111","volume":"20","author":[{"given":"F.","family":"Ahmad","sequence":"first","affiliation":[{"name":"Department of Haematology All India Institute of Medical Sciences (AIIMS) New Delhi India"},{"name":"Center for Translational Medicine School of Medicine Temple University Philadelphia PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F.","family":"Oyen","sequence":"additional","affiliation":[{"name":"Department of Pediatric Haematology Oncology University Medical Centre Hamburg Eppendorf Hamburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.","family":"Jan","sequence":"additional","affiliation":[{"name":"Department of Haematology All India Institute of Medical Sciences (AIIMS) New Delhi India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"U.","family":"Budde","sequence":"additional","affiliation":[{"name":"H\u00e4mostaseology Medilys Laborgesellschaft mbH Hamburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.","family":"Schneppenheim","sequence":"additional","affiliation":[{"name":"Department of Pediatric Haematology Oncology University Medical Centre Hamburg Eppendorf Hamburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.","family":"Saxena","sequence":"additional","affiliation":[{"name":"Department of Haematology All India Institute of Medical Sciences (AIIMS) New Delhi 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