{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T10:01:56Z","timestamp":1753869716087,"version":"3.41.2"},"reference-count":12,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,12,28]],"date-time":"2021-12-28T00:00:00Z","timestamp":1640649600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["2015\u201002957"],"award-info":[{"award-number":["2015\u201002957"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>One of the challenges of genetic testing in patients with hemophilia A is the interpretation of sequence variants. Here we report a silent variant found in exon 2 in the <jats:italic>F8<\/jats:italic> gene in a 47\u2010year\u2010old patient with a previous von Willebrand disease (VWD) type 1 diagnosis. Clinically he had mild bleeding symptoms restricted to prolonged bleeding from minor wounds. Sanger sequencing of <jats:italic>F8<\/jats:italic> gene using genomic DNA showed a hemizygous silent variant in exon 2: c.222G&gt;T, p.Thr74Thr. When applying ACMG criteria, the variant was predicted to be \u201clikely benign\u201d in the analyzing software or VUS after curating. Sanger sequencing of the patient's cDNA after nested polymerase chain reaction showed that the patient had both a normal transcript containing exons 1\u20134 and a defect transcript lacking exon 2. These findings explain the patient's low FVIII:C level and led to the diagnosis of mild hemophilia A instead of VWD type 1. This case illustrates that mRNA work\u2010up may be needed to clarify a patient's phenotype\u2013genotype.<\/jats:p>","DOI":"10.1002\/mgg3.1856","type":"journal-article","created":{"date-parts":[[2021,12,28]],"date-time":"2021-12-28T13:29:56Z","timestamp":1640698196000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Silent variant in <i>F8<\/i>:c.222G&gt;T (p.Thr74Thr) causes a partial exon skipping in a patient with mild hemophilia A"],"prefix":"10.1002","volume":"10","author":[{"given":"Anna","family":"Letelier","sequence":"first","affiliation":[{"name":"Department of Clinical Sciences Lund (IKVL)\u2014Pediatrics Lund University Lund Sweden"},{"name":"Department for Molecular Diagnostics Clinical Genetics Hemophilia Laboratory, Region Sk\u00e5ne Sk\u00e5ne University Hospital Lund Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rolf","family":"Ljung","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences Lund (IKVL)\u2014Pediatrics Lund University Lund Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9974-4880","authenticated-orcid":false,"given":"Anna","family":"Olsson","sequence":"additional","affiliation":[{"name":"Department of Medicine Region V\u00e4stra G\u00f6taland Sahlgrenska University Hospital Gothenburg Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6058-8350","authenticated-orcid":false,"given":"Nadine G.","family":"Andersson","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences Lund (IKVL)\u2014Pediatrics Lund University Lund Sweden"},{"name":"Department of Pediatric Hematology and Oncology, Region Sk\u00e5ne Sk\u00e5ne University Hospital Lund Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,12,28]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13353-018-0444-7"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkg616"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2005.01140.x"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2013.176"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2308-7"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bty897"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.12562"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.13947"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-020-0766-9"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/317726a0"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.12039"}],"container-title":["Molecular Genetics &amp; Genomic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.1856","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mgg3.1856","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.1856","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T03:18:01Z","timestamp":1693192681000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mgg3.1856"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,28]]},"references-count":12,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,1]]}},"alternative-id":["10.1002\/mgg3.1856"],"URL":"https:\/\/doi.org\/10.1002\/mgg3.1856","archive":["Portico"],"relation":{},"ISSN":["2324-9269","2324-9269"],"issn-type":[{"type":"print","value":"2324-9269"},{"type":"electronic","value":"2324-9269"}],"subject":[],"published":{"date-parts":[[2021,12,28]]},"assertion":[{"value":"2021-09-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-12-14","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-12-28","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e1856"}}