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.

中文翻译：

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根据 ACMG/AMP 指南分类的 PedNet 血友病登记处的新型 F8 和 F9 基因变体。

在血友病 A 和 B 中，对F8和F9基因变异的分析能够实现携带者和产前诊断以及预测抑制剂发展的风险。PedNet Registry 前瞻性地收集了 2000 多名血友病儿童的临床、遗传和表型数据。F8/F9基因变异的遗传报告被统一归类到人类基因组变异协会的命名法，并使用国际人口和疾病特定数据库、文献调查以及适用的计算预测程序重新评估。我们报告了F8和F9中的 88 个新变体基因，80 个符合第 5 类（致病性）的标准，6 个符合第 4 类（可能致病）的标准和两个符合美国医学遗传学和基因组学/分子病理学会指南的第 3 类（意义不明的变异）标准以及信息关于各自的表型和抑制剂的形成。该研究强调需要重新评估和更新较早的血友病遗传报告，无论是在本地还是在变异数据库中，都要根据命名法和新指南的变化。