Factor X (FX) deficiency is a rare autosomal recessive disorder. The phenotype and genotype of 15 Iranian patients with FX deficiency from 13 unrelated families with a high frequency of consanguinity were analysed. Five different assays identified four patients from three families with a discrepancy between low-FX coagulant activity (FX:C) and higher-FX antigen (FX:Ag) (a type II deficiency). The remaining 11 patients had parallel reductions of FX:C and FX:Ag (a type I deficiency). Nine different homozygous candidate mutations were identified, of which eight were novel. The four type II cases were associated with an Arg()1)Thr missense mutation in the prepropeptide: Arg()1) is highly conserved in all vitamin K-dependent proteins. Four type I mutations (Gly78Asp, Cys81Tyr, Gly94Arg and Asp95Glu) were localized to the EGF-1 and EGF-2 domains, for which molecular views showed that the protein folding would be disrupted. The type I mutation Gly222Asp was localized in the catalytic domain of FX, and is sufficiently close to the Asp-His-Ser catalytic triad to disrupt its correct protein folding. The two type I splice site mutations were IVS1+3, A fi T and IVS2–3, T fi G. These novel homozygous FX mutations were consistent with their phenotypes and agree with experimental data from knockout mice, indicating that FX is an essential protein for survival.
Gene mutations and three-dimensional structural analysis in 13 families with severe factor X deficiency / F. Peyvandi, M. Menegatti, E. Santagostino, S. Akhavan, J. Uprichard, D.J. Perry, S.J. Perkins, P.M. Mannucci. - In: BRITISH JOURNAL OF HAEMATOLOGY. - ISSN 0007-1048. - 117:3(2002 Jun), pp. 685-692.
|Titolo:||Gene mutations and three-dimensional structural analysis in 13 families with severe factor X deficiency|
PAYVANDI, FLORA (Primo)
MENEGATTI, MARZIA (Secondo)
MANNUCCI, PIER MANNUCCIO (Ultimo)
|Parole Chiave:||FX deficiency; FX deficiency phenotype analysis; FX mutations|
|Settore Scientifico Disciplinare:||Settore MED/09 - Medicina Interna|
|Data di pubblicazione:||giu-2002|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1046/j.1365-2141.2002.03486.x|
|Appare nelle tipologie:||01 - Articolo su periodico|