دورية أكاديمية
أعرض في EDS

Application of whole-exome sequencing to direct the specific functional testing and diagnosis of rare inherited bleeding disorders in patients from the Öresund Region, Scandinavia.

التفاصيل البيبلوغرافية
العنوان: Application of whole-exome sequencing to direct the specific functional testing and diagnosis of rare inherited bleeding disorders in patients from the Öresund Region, Scandinavia.
المؤلفون: Leinøe E; Department of Haematology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark., Zetterberg E; Department of Haematology, Coagulation Unit, Skaane University Hospital, Lund, Sweden., Kinalis S; Centre for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark., Østrup O; Centre for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark., Kampmann P; Department of Haematology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark., Norström E; Department of Translational Medicine, Lund University, Skaane University Hospital, Lund, Sweden., Andersson N; Department of Haematology, Coagulation Unit, Skaane University Hospital, Lund, Sweden., Klintman J; Department of Haematology, Coagulation Unit, Skaane University Hospital, Lund, Sweden., Qvortrup K; Department of Biomedical Sciences, Core Facility for Integrated Microscopy (CFIM), University of Copenhagen, Copenhagen, Denmark., Nielsen FC; Centre for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark., Rossing M; Centre for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
المصدر: British journal of haematology [Br J Haematol] 2017 Oct; Vol. 179 (2), pp. 308-322. Date of Electronic Publication: 2017 Jul 27.
نوع المنشور: Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 0372544 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1365-2141 (Electronic) Linking ISSN: 00071048 NLM ISO Abbreviation: Br J Haematol Subsets: MEDLINE
أسماء مطبوعة: Publication: Oxford : Wiley-Blackwell
Original Publication: Oxford : Blackwell Scientific Publications
مواضيع طبية MeSH: Exome* , Germ-Line Mutation*, Blood Coagulation Disorders, Inherited/*diagnosis , Blood Coagulation Disorders, Inherited/*genetics, Blood Coagulation Disorders, Inherited/epidemiology ; Denmark/epidemiology ; Female ; Genome-Wide Association Study ; Humans ; Male ; Sweden/epidemiology
مستخلص: Rare inherited bleeding disorders (IBD) are a common cause of bleeding tendency. To ensure a correct diagnosis, specialized laboratory analyses are necessary. This study reports the results of an upfront diagnostic strategy using targeted whole exome sequencing. In total, 156 patients with a significant bleeding assessment tool score participated in the study, of which a third had thrombocytopenia. Eighty-seven genes specifically associated with genetic predisposition to bleeding were analysed by whole exome sequencing. Variants were classified according to the five-tier scheme. We identified 353 germline variants. Eight patients (5%) harboured a known pathogenic variant. Of the 345 previously unknown variants, computational analyses predicted 99 to be significant. Further filtration according to the Mendelian inheritance pattern, resulted in 59 variants being predicted to be clinically significant. Moreover, 34% (20/59) were assigned as novel class 4 or 5 variants upon targeted functional testing. A class 4 or 5 variant was identified in 30% of patients with thrombocytopenia (14/47) versus 11% of patients with a normal platelet count (12/109) (P < 0·01). An IBD diagnosis has a major clinical impact. The genetic investigations detailed here extricated our patients from a diagnostic conundrum, thus demonstrating that continuous optimization of the diagnostic work-up of IBD is of great benefit.
(© 2017 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.)
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فهرسة مساهمة: Keywords: bleeding disorders; genetic analysis; platelet disorders
تواريخ الأحداث: Date Created: 20170728 Date Completed: 20171019 Latest Revision: 20220321
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC5655919
DOI: 10.1111/bjh.14863
PMID: 28748566
قاعدة البيانات: MEDLINE
الوصف
تدمد:1365-2141
DOI:10.1111/bjh.14863