What is the pathophysiology of congenital factor X deficiency?

Updated: Mar 23, 2018
  • Author: Robert A Schwartz, MD, MPH; Chief Editor: Perumal Thiagarajan, MD  more...
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Answer

Several specific mutations have been reported. [12] Relatively recently identified mutations include Gly366Ser, Arg347His, Phe31Ser, Gly133Arg, Val196Met, Gly204Arg, Glu51Lys, and Cys364Arg. [14, 15, 16, 17, 18, 19, 20] Mutations in the Gla-domain of factor X, a 39 residue peptide that is part of its light chain, have been documented in at least 15 cases of factor X deficiency. [21]

In a Japanese patient with factor X deficiency, molecular analysis revealed a homozygous glutamine-to-glycine mutation at residue 32, which normally undergoes gamma-carboxylation within the gamma-carboxyglutamic acid–rich domain. [22] A factor X–deficient woman from France was identified as homozygous for a mutation in exon VIII, resulting in the substitution of serine 334 by proline. [23] This mutation is probably responsible for altering the orientation of the cleavage site of factor X, preventing activation of the molecule. Other reported consequences of this mutation include interference with protein folding, disruption of disulfide bonds, and inhibition of factor binding sites.

Factor X has a natural variant carrying the Asp-185 deletion. Paradoxically, this variant may be associated with only mild bleeding despite a severe factor X deficiency. [24]


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