{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T16:03:03Z","timestamp":1792166583790,"version":"4.4.0"},"reference-count":22,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2014,9,6]],"date-time":"2014-09-06T00:00:00Z","timestamp":1409961600000},"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":[[2014,11]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>The paper describes the experience of the Genetic Diagnostic Laboratory in prenatal testing for haemophilia A, an X\u2010linked recessive disease caused by mutations in the <jats:italic>F<\/jats:italic>8 gene. Knowledge of a familial mutation prior to pregnancy can benefit prenatal diagnosis and decrease wait time for molecular testing during pregnancy. This is a retrospective review of a series of pregnant women who pursued <jats:italic>F<\/jats:italic>8 gene testing from December 1997 through May 2012, highlighting three cases, which demonstrate the technical complexities of analysis and the implications of not knowing carrier status prior to pregnancy. Mutations of the <jats:italic>F<\/jats:italic>8 gene were detected in affected males, obligate female carriers and suspected female carriers by <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> sequencing, inverse\u2010<jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content>, qRT\u2010<jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content>, Southern blot and exonic dosage analysis. The same methods were used to analyse prenatal samples from obligate or suspected female carriers upon request. Maternal cell contamination studies were performed for all prenatal samples analysed. Ninety\u2010nine women pursued <jats:italic>F<\/jats:italic>8 testing during pregnancy, either for carrier status alone or carrier status and prenatal diagnosis. Ninety\u2010one women (91%) requested carrier testing because they did not know their <jats:italic>F<\/jats:italic>8 mutation carrier status prior to pregnancy. Eight women requested prenatal diagnosis only, and only 4 of these were aware of their mutation status. Thirty\u2010seven individuals were found to be mutation carriers. Forty\u2010two prenatal samples were received for prenatal diagnosis. In total 21 foetuses were identified as mutation carriers. Mutation detection was complex and increased the turnaround time in some cases. Only four of 99 women who submitted samples for <jats:italic>F<\/jats:italic>8 testing were aware of their <jats:italic>F<\/jats:italic>8 mutation status prior to pregnancy. Knowledge of <jats:italic>F<\/jats:italic>8 mutation status prior to pregnancy allows for efficient prenatal diagnosis, when desired. Thus, preconception genetic counselling is required to inform patients of the available options and the complex and time\u2010consuming nature of <jats:italic>F<\/jats:italic>8 testing.<\/jats:p>","DOI":"10.1111\/hae.12517","type":"journal-article","created":{"date-parts":[[2014,9,6]],"date-time":"2014-09-06T06:05:01Z","timestamp":1409983501000},"source":"Crossref","is-referenced-by-count":20,"title":["Prenatal diagnosis in haemophilia A: experience of the genetic diagnostic laboratory"],"prefix":"10.1111","volume":"20","author":[{"given":"L.","family":"Kessler","sequence":"first","affiliation":[{"name":"The Genetic Diagnostic Laboratory Department of Genetics Perelman School of Medicine The University of Pennsylvania Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Adams","sequence":"additional","affiliation":[{"name":"The Genetic Diagnostic Laboratory Department of Genetics Perelman School of Medicine The University of Pennsylvania Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Mighion","sequence":"additional","affiliation":[{"name":"The Genetic Diagnostic Laboratory Department of Genetics Perelman School of Medicine The University of Pennsylvania Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Walther","sequence":"additional","affiliation":[{"name":"The Genetic Diagnostic Laboratory Department of Genetics Perelman School of Medicine The University of Pennsylvania Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Ganguly","sequence":"additional","affiliation":[{"name":"The Genetic Diagnostic Laboratory Department of Genetics Perelman School of Medicine The University of Pennsylvania Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,9,6]]},"reference":[{"key":"e_1_2_9_2_1","first-page":"778","article-title":"Analysis of large structural changes of the factor VIII gene, involving intron 1 and 22, in severe hemophilia A","volume":"88","author":"Andrikovics H","year":"2003","journal-title":"Haematologica"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0b013e318214780e"},{"issue":"1","key":"e_1_2_9_4_1","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1182\/blood.V99.1.168","article-title":"Recurrent inversion breaking intron 1 of the factor VIII gene is a frequent cause of severe hemophilia A","volume":"99","author":"Bagnall RD","journal-title":"Blood"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.12219"},{"key":"e_1_2_9_6_1","first-page":"1","article-title":"The importance of genetic testing","author":"Butler R","year":"2013","journal-title":"Care Matters"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2010.08545.x"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2007.01561.x"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.10119"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-09-379453"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2011.107"},{"key":"e_1_2_9_12_1","volume-title":"GeneReviews\u00ae [Internet]","author":"Konkle BA","year":"1993"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2006.01277.x"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1193-236"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.12427"},{"key":"e_1_2_9_16_1","unstructured":"National Hemophilia Foundation.My Life Our Future 2014.http:\/\/www.mylifeourfuture.org\/. 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