Gene mutations and three-dimensional structural analysis in 13 families with severe factor X deficiency
Articolo
Data di Pubblicazione:
2002
Citazione:
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.
Abstract:
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.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
FX deficiency; FX deficiency phenotype analysis; FX mutations
Elenco autori:
F. Peyvandi, M. Menegatti, E. Santagostino, S. Akhavan, J. Uprichard, D.J. Perry, S.J. Perkins, P.M. Mannucci
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