{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:47:51Z","timestamp":1790729271422,"version":"4.1.0"},"reference-count":38,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2017,5,5]],"date-time":"2017-05-05T00:00:00Z","timestamp":1493942400000},"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":[[2017,7]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Genomic inversions are usually balanced, but unusual patterns have been described in haemophilia A (<jats:styled-content style=\"fixed-case\">HA<\/jats:styled-content>) patients for intron 22 (Inv22) and intron 1 (Inv1) inversions leading to the hypothesis of more complex rearrangements involving deletions or duplications.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>To characterize five abnormal patterns either in Southern blot and long\u2010range <jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content> for Inv22 or in <jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content> for Inv1.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>All patients were studied using cytogenetic microarray analysis (<jats:styled-content style=\"fixed-case\">CMA<\/jats:styled-content>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In all cases, <jats:styled-content style=\"fixed-case\">CMA<\/jats:styled-content> analysis found that each inversion was associated with complex Xq28 rearrangement. In three patients, <jats:styled-content style=\"fixed-case\">CMA<\/jats:styled-content> analysis showed large duplication ranging from 230 to 1302 kb and encompassing a various number of contiguous genes among which <jats:italic><jats:styled-content style=\"fixed-case\">RAB<\/jats:styled-content>39B<\/jats:italic>. <jats:italic><jats:styled-content style=\"fixed-case\">RAB<\/jats:styled-content>39B<\/jats:italic> duplication is a strong candidate gene for X\u2010linked intellectual disability (<jats:styled-content style=\"fixed-case\">XLID<\/jats:styled-content>). Surprisingly, none of the severe <jats:styled-content style=\"fixed-case\">HA<\/jats:styled-content> patients with <jats:italic><jats:styled-content style=\"fixed-case\">RAB<\/jats:styled-content>39B<\/jats:italic> duplication reported in this study or in the literature exhibited <jats:styled-content style=\"fixed-case\">XLID<\/jats:styled-content>. We hypothesise that <jats:italic>F8<\/jats:italic> complex rearrangement down regulated <jats:italic><jats:styled-content style=\"fixed-case\">RAB<\/jats:styled-content>39B<\/jats:italic> expression. In the two remaining patients, <jats:styled-content style=\"fixed-case\">CMA<\/jats:styled-content> analysis found Xq28 large deletion (from 285 to 522 kb). Moyamoya syndrome was strongly suspected in one of them who carried <jats:italic><jats:styled-content style=\"fixed-case\">BRCC<\/jats:styled-content>3<\/jats:italic> deletion.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Because several <jats:italic>F8<\/jats:italic> neighbouring genes are associated with other pathologies such as <jats:styled-content style=\"fixed-case\">XLID<\/jats:styled-content> and cardiovascular disease, all <jats:styled-content style=\"fixed-case\">HA<\/jats:styled-content> patients where complex Xq28 rearrangement was suspected should be referred to a geneticist for possible utility of a pangenomic study. Such investigation should be carefully considered in genetic counselling in female carriers to assess the risk of transmitting severe <jats:styled-content style=\"fixed-case\">HA<\/jats:styled-content> with a \u201ccontiguous gene syndrome\u201d.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hae.13218","type":"journal-article","created":{"date-parts":[[2017,5,5]],"date-time":"2017-05-05T13:02:58Z","timestamp":1493989378000},"source":"Crossref","is-referenced-by-count":13,"title":["Molecular cytogenetic characterization of five <i>F8<\/i> complex rearrangements: utility for haemophilia A genetic counselling"],"prefix":"10.1111","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7408-6474","authenticated-orcid":false,"given":"Y.","family":"Jourdy","sequence":"first","affiliation":[{"name":"Hospices Civils de Lyon H\u00f4pital Edouard Herriot Service d'h\u00e9matologie Biologique Lyon France"},{"name":"Univ Lyon EA 4609 H\u00e9mostase et cancer Universit\u00e9 Claude Bernard Lyon 1 Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Chatron","sequence":"additional","affiliation":[{"name":"Hospices Civils de Lyon Groupe Hospitalier Est Laboratoire de Cytog\u00e9n\u00e9tique Constitutionnelle Bron France"},{"name":"Univ Lyon CRNL \u00e9quipe GENDEV INSERM U1028 CNRS UMR5292 Universit\u00e9 Claude Bernard Lyon 1 Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Fretigny","sequence":"additional","affiliation":[{"name":"Hospices Civils de Lyon H\u00f4pital Edouard Herriot Service d'h\u00e9matologie Biologique Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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