A new mutation (Arg251Trp) in the Ca2+ binding site of factor X protease domain appears to be responsible for the defect in the extrinsic pathway activation of factor X Padua.
Factor X Padua, first described a few years ago, is characterized by a defect only in the extrinsic system. In this present paper, the molecular basis for this peculiar defect is investigated. Polymerase chain reaction amplification and direct sequencing of the entire FX coding sequence and of exon-intron junctions detected in the proposita a C-to-T translocation in exon 8 of nucleotide 875 at the homozygous level. This resulted in the substitution of tryptophan for arginine 251. A niece of the proposita was shown to be heterozygous for the abnormality. Molecular modeling suggested that the mutation does not alter significantly folding and stability of the protein but may be involved in the Ca2+ binding site.
Department of Medical and Surgical Sciences, Second Chair of Medicine, via Ospedale 105, University of Padua Medical School, 35121 Padua, Italy. antonio.girolami@unipd.it
Antonio
A
Girolami
Fabrizio
F
Vianello
Laura
L
Cabrio
Anna Maria
AM
Lombardi
D001665:Binding Sites / Q000235:genetics; D001778:Blood Coagulation Disorders / Q000235:genetics*; D002118:Calcium / Q000378:metabolism; D005170:Factor X / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D005192:Family Health; D005260:Female; D006801:Humans; D008875:Middle Aged; D008958:Models, Molecular; D020125:Mutation, Missense; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
C492929:factor X Padua; D005170:Factor X; D002118:Calcium