Identification of 217 unreported mutations in the F8 gene in a group of 1,410 unselected Italian patients with hemophilia A

R. Santacroce, M. Acquila, D. Belvini, G. Castaldo, I. Garagiola, S. H. Giacomelli, A. M. Lombardi, B. Minuti, F. Riccardi, R. Salviato, L. Tagliabue, E. Grandone, M. Margaglione

Research output: Contribution to journalArticlepeer-review

Abstract

To provide a National database, 1,410 unrelated hemophilia A (HA) patients were investigated using screening methods denaturing high-performance liquid chromatography (DHPLC), conformational-sensitive gel electrophoresis (CSGE)] and/or direct sequencing. F8 gene mutations were identified in 877 (81%), 146 (82%), and 133 (89%) families with severe, moderate, or mild HA, respectively. Among the 382 different mutations detected, 217 (57%) have not previously been reported in the F8 Haemophilia A Mutation, Structure, Test and Resource Site (HAMSTeRS) database. Mutations leading to a null allele accounted for 82, 15%, and less than 1% of severe, moderate, or mild HA, respectively. A missense mutation was identified in 16%, 68%, and 81% of severe, moderate, or mild HA, respectively. They included 105 missense mutations (48%), 41 small deletions (19%), 25 splice site mutations (12%), 24 nonsense mutations (11%), 18 insertions (8%), three large deletions (1%), and one deletion plus insertion. Unreported mutations were distributed throughout the F8 gene, as they affected all F8 exons but exon 20. We report a wide spectrum of mutations collected in a large National database. The type of mutation was a strong predictor of the clinical phenotype. This database is expected to considerably improve the genetic counseling and medical care of HA families in Italy.

Original languageEnglish
Pages (from-to)275-284
Number of pages10
JournalJournal of Human Genetics
Volume53
Issue number3
DOIs
Publication statusPublished - Mar 2008

Keywords

  • F8 gene
  • Hemophilia A
  • Mutations
  • Phenotype

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

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