Novel F8 and F9 gene variants from the PedNet Hemophilia Registry classified according to ACMG/AMP guidelines

Research output: Contribution to journalArticle

Abstract

In hemophilia A and B, analysis of the F8 and F9 gene variants enables carrier- and prenatal diagnosis and prediction of risk for development of inhibitors. The PedNet Registry collects clinical, genetic and phenotypic data prospectively on >2000 children with hemophilia. The genetic reports of F8/F9 gene variants were classified uniformly to HGVS nomenclature and re-evaluated using international population- and disease-specific databases, literature survey and, where applicable, computational predictive programs. We report 88 novel variants in the F8 and F9 genes, 80 fulfilling criteria for class 5 (pathogenic), six for class 4 (likely pathogenic) and two fulfilling criteria for class 3 (variant of unknown significance) of the ACMG (American College of Medical Genetics and Genomics)/AMP (Association for Molecular Pathology) guidelines together with information on the respective phenotype and inhibitor formation. The study highlights the need to re-evaluate and update earlier genetic reports in hemophilia both locally but also in variant databases in the light of changed nomenclature and new guidelines. This article is protected by copyright. All rights reserved.

Details

Authors
Organisations
External organisations
  • Maggiore Hospital Policlinico
  • University Hospitals Leuven
  • Skåne University Hospital
  • Klinikum Bremen-Mitte
  • University Medical Center Utrecht
  • University of Bern
  • Helsinki University Central Hospital
  • Aarhus University Hospital
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Hematology
  • Pediatrics
Original languageEnglish
JournalHuman Mutation
Publication statusE-pub ahead of print - 2020 Sep 15
Publication categoryResearch
Peer-reviewedYes

Bibliographic note

This article is protected by copyright. All rights reserved.