{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T05:02:18Z","timestamp":1761541338813,"version":"3.44.0"},"reference-count":42,"publisher":"BMJ","issue":"8","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Clin Pathol"],"accepted":{"date-parts":[[2016,12,14]]},"published-print":{"date-parts":[[2017,8]]},"abstract":"<jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>The frequency of X chromosome pericentric inversion is much less than that of autosome chromosome. We hereby characterise a pericentric inversion of X chromosome associated with severe factor VIII (FVIII) deficiency in a sporadic haemophilia A (HA) pedigree.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>PCR primer walking and genome walking strategies were adopted to identify the exact breakpoints of the inversion. Copy number variations (CNVs) of the <jats:italic>F8<\/jats:italic> and the whole chromosomes were detected by AccuCopy and Affymetrix CytoScan High Definition (HD) assays, respectively. A karyotype analysis was performed by cytogenetic G banding technique.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We identified a previously undescribed type of pericentric inversion of the X chromosome [inv(X)(p11.21q28)] in the proband with FVIII:C &lt;1%. One breakpoint was located in the intron 7 of the <jats:italic>F<\/jats:italic>8, which disrupted the transcription of the <jats:italic>F8,<\/jats:italic> and the other located in the upstream of the <jats:italic>PFKFB1<\/jats:italic> of the X chromosome. The inversion segment was approximately 64.4% of the total chromosomal length. The karyotype analysis of the X chromosome confirmed the pericentric inversion of the X chromosome in the proband and his mother. A haplotype analysis traced the inversion to his maternal grandfather, who was not a somatic mosaic of the inversion. This finding indicated that the causative mutation may originate from his germ cells or a rare possibility of germ-cell mosaicism.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The characterisation of pericentric inversion involving <jats:italic>F8<\/jats:italic> extended the molecular mechanisms causing HA. The pericentric inversion rearrangement involves <jats:italic>F8<\/jats:italic> by non-homologous end joining is responsible for pathogensis of severe HA.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jclinpath-2016-204050","type":"journal-article","created":{"date-parts":[[2017,1,10]],"date-time":"2017-01-10T22:00:42Z","timestamp":1484085642000},"page":"656-661","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["A pericentric inversion of chromosome X disrupting <i>F8<\/i> and resulting in haemophilia A"],"prefix":"10.1136","volume":"70","author":[{"given":"Yu","family":"Xin","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, The Fourth Affiliated Hospital, Harbin Medical University, Harbin, China"},{"name":"State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 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