TY - JOUR
T1 - Analysis of 18 novel mutations in the factor VIII gene
AU - Bicocchi, Maria Patrizia
AU - Pasino, Mirella
AU - Lanza, Tiziana
AU - Bottini, Federico
AU - Boeri, Elio
AU - Mori, Pier G.
AU - Molinari, Angelo C.
AU - Rosano, Camillo
AU - Acquila, Maura
PY - 2003/9
Y1 - 2003/9
N2 - We describe 18 novel mutations, unreported in the Haemophilia A mutation Databases, that have been identified in a cohort of unrelated. Italian patients affected with haemophilia A (HA). Screening of the factor VIII gene (FVIII) was performed using denaturing high-performance liquid chromatography (DHPLC) and direct sequencing. Eight mutations were characterized as non-missense alterations, and the remaining 10 were missense mutations. Heterozygosity for the identified mutations was observed in the female relatives of patients belonging to eight families with sporadic cases. In an attempt to understand better the causative effect of the mutations and the clinical variability of the patients, missense mutation consequences were investigated for: (1) the nature of the new amino acid: (2) the location of the substituted amino acid within crystallographic and theoretical models: and (3) the degree of conservation of the native residue in factor VIII (FVIII) protein and FVIII-related protein family aligned sequences. These research tools have provided evidence that the mutations we describe involve residues that were conserved, at least in FVIII proteins, in all the species we compared.
AB - We describe 18 novel mutations, unreported in the Haemophilia A mutation Databases, that have been identified in a cohort of unrelated. Italian patients affected with haemophilia A (HA). Screening of the factor VIII gene (FVIII) was performed using denaturing high-performance liquid chromatography (DHPLC) and direct sequencing. Eight mutations were characterized as non-missense alterations, and the remaining 10 were missense mutations. Heterozygosity for the identified mutations was observed in the female relatives of patients belonging to eight families with sporadic cases. In an attempt to understand better the causative effect of the mutations and the clinical variability of the patients, missense mutation consequences were investigated for: (1) the nature of the new amino acid: (2) the location of the substituted amino acid within crystallographic and theoretical models: and (3) the degree of conservation of the native residue in factor VIII (FVIII) protein and FVIII-related protein family aligned sequences. These research tools have provided evidence that the mutations we describe involve residues that were conserved, at least in FVIII proteins, in all the species we compared.
KW - Denaturing high-performance liquid chromatography mutation analysis
KW - Factor VIII
KW - Genotype-phenotype
KW - Haemophilia A
KW - Network Protein Sequence Analysis (NPSA)web server
UR - http://www.scopus.com/inward/record.url?scp=0041410234&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0041410234&partnerID=8YFLogxK
U2 - 10.1046/j.1365-2141.2003.04494.x
DO - 10.1046/j.1365-2141.2003.04494.x
M3 - Article
C2 - 12930394
AN - SCOPUS:0041410234
VL - 122
SP - 810
EP - 817
JO - British Journal of Haematology
JF - British Journal of Haematology
SN - 0007-1048
IS - 5
ER -