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

PedNet Study Group, Nadine G. Andersson, Veerle Labarque, Anna Letelier, Maria Elisa Mancuso, Martina Bührlen, Kathelijn Fischer, Mutlu Kartal-Kaess, Minna Koskenvuo, Torben Mikkelsen, Rolf Ljung

Research output: Contribution to journalArticlepeer-review

Abstract

In hemophilia A and B, analysis of the F8 and F9 gene variants enables carrier and prenatal diagnosis and prediction of risk for the development of inhibitors. The PedNet Registry collects clinical, genetic, and phenotypic data prospectively on more than 2000 children with hemophilia. The genetic reports of F8/F9 gene variants were classified uniformly to Human Genome Variation Society nomenclature and reevaluated 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 American College of Medical Genetics and Genomics/Association for Molecular Pathologyguidelines together with information on the respective phenotype and inhibitor formation. The study highlights the need to reevaluate and update earlier genetic reports in hemophilia both locally but also in variant databases in light of changed nomenclature and new guidelines.

Original languageEnglish
Pages (from-to)2058-2072
Number of pages15
JournalHuman Mutation
Volume41
Issue number12
DOIs
Publication statusPublished - Dec 1 2020

Keywords

  • F8 gene
  • F9 gene
  • Factor IX
  • Factor VIII
  • hemophilia
  • variant database

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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