TY - JOUR
T1 - Identification of 217 unreported mutations in the F8 gene in a group of 1,410 unselected Italian patients with hemophilia A
AU - Santacroce, R.
AU - Acquila, M.
AU - Belvini, D.
AU - Castaldo, G.
AU - Garagiola, I.
AU - Giacomelli, S. H.
AU - Lombardi, A. M.
AU - Minuti, B.
AU - Riccardi, F.
AU - Salviato, R.
AU - Tagliabue, L.
AU - Grandone, E.
AU - Margaglione, M.
PY - 2008/3
Y1 - 2008/3
N2 - 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.
AB - 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.
KW - F8 gene
KW - Hemophilia A
KW - Mutations
KW - Phenotype
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U2 - 10.1007/s10038-007-0238-y
DO - 10.1007/s10038-007-0238-y
M3 - Article
C2 - 18217193
AN - SCOPUS:40049086790
VL - 53
SP - 275
EP - 284
JO - Journal of Human Genetics
JF - Journal of Human Genetics
SN - 1434-5161
IS - 3
ER -