Studio
Coordinatori dello studio
Giancarlo Castaman, Firenze
Elena Santagostino, Milano
Obiettivo dello studio è identificare mutazioni del gene F8 in pazienti italiani con emofilia A lieve.
Lo studio è in corso.
Il centro emofilia coordinatore ha ottenuto l’approvazione del comitato etico.
Abstract
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 – The AICE-Genetics Study Group
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.
J Hum Genet (2008) 53:275″“284 DOI 10.1007/s10038-007-0238-y