دورية أكاديمية
أعرض في EDS

Genetic screening of children with suspected inherited bleeding disorders.

التفاصيل البيبلوغرافية
العنوان: Genetic screening of children with suspected inherited bleeding disorders.
المؤلفون: Andersson NG; Department of Clinical Sciences, Paediatrics, Lund University, Lund, Sweden.; Centre for Thrombosis and Haemostasis, Skåne University Hospital, Malmö, Sweden.; Department for Paediatric Haematology and Oncology, Skåne University Hospital, Malmö, Sweden., Rossing M; Centre for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark., Fager Ferrari M; Centre for Thrombosis and Haemostasis, Skåne University Hospital, Malmö, Sweden.; Department of Translational Medicine, Lund University, Malmö, Sweden., Gabrielaite M; Centre for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark., Leinøe E; Department of Haematology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark., Ljung R; Department of Clinical Sciences, Paediatrics, Lund University, Lund, Sweden., Mårtensson A; Department of Clinical Sciences, Paediatrics, Lund University, Lund, Sweden.; Department for Paediatric Haematology and Oncology, Skåne University Hospital, Malmö, Sweden., Norström E; Department for Clinical Chemistry, Skåne University Hospital, Malmö, Sweden., Zetterberg E; Centre for Thrombosis and Haemostasis, Skåne University Hospital, Malmö, Sweden.; Department of Translational Medicine, Lund University, Malmö, Sweden.
المصدر: Haemophilia : the official journal of the World Federation of Hemophilia [Haemophilia] 2020 Mar; Vol. 26 (2), pp. 314-324. Date of Electronic Publication: 2020 Feb 26.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Blackwell Science Country of Publication: England NLM ID: 9442916 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1365-2516 (Electronic) Linking ISSN: 13518216 NLM ISO Abbreviation: Haemophilia Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Osney Mead, Oxford, UK : Blackwell Science, [1994-
مواضيع طبية MeSH: Blood Coagulation Disorders, Inherited/*diagnosis , Blood Coagulation Disorders, Inherited/*genetics , Genetic Predisposition to Disease/*genetics , Genetic Testing/*methods, Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Infant, Newborn ; Male
مستخلص: Introduction: Genetic screening using high-throughput DNA sequencing has become a tool in diagnosing patients with suspected inherited bleeding disorders (IBD). However, its usefulness and diagnostic efficacy in children is unclear.
Aim: To evaluate the diagnostic efficacy of genetic screening for IBD in children and downstream further testing.
Methods: After informed consent, children (<18 years) with suspected IBD underwent genetic screening with 94 selected genes.
Results: A total of 68 heterozygous class 3-5 variants were detected in 30 children, 2.3 variants per patient. Directed specific functional testing was performed after genetic screening in a subset of patients. Adhering to the ACMG guidelines, the results of functional testing together with family history and previous publications classified three variants as likely disease causing (class 4) and two variants as disease causing (class 5), all in children with thrombocytopenia. The overall diagnostic rate was 16.7% (5/30). Children with thrombocytopenia had a significantly higher rate of significant genetic findings, 5/9 (55.6%) vs. 0/21 (0%; P = .0009).
Conclusion: We conclude that performing genetic screening in children is an effective tool especially for children with inherited thrombocytopenia and has the possibility to diagnose platelet disorders adequately early in life. Children with bleeding diathesis, normal coagulation work-up and without thrombocytopenia are unlikely to be diagnosed by genetic screening. Ethical issues such as incidental findings, variants associated with cancer and the interpretation of the genetic results into clinical practice remain problematic.
(© 2020 The Authors. Haemophilia published by John Wiley & Sons Ltd.)
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فهرسة مساهمة: Keywords: bleeding disorders; gene arrays; genetics of thrombosis and haemostasis; paediatric haematology; platelet disorders; platelet genetic disorders
تواريخ الأحداث: Date Created: 20200227 Date Completed: 20201102 Latest Revision: 20201102
رمز التحديث: 20240628
DOI: 10.1111/hae.13948
PMID: 32100410
قاعدة البيانات: MEDLINE
الوصف
تدمد:1365-2516
DOI:10.1111/hae.13948