The clinical and laboratory significance of cases of congenital FX deficiency due to defects in the Gla-domain.
The Gla-domain of factor X (FX) is a 39 residue peptide, part of the light chain, and is characterized by the presence of 11 gamma-carboxylglutaminic acid residues interspersed among other no-Gla residues. At least 15 cases of FX deficiency have been shown to be mutated in this area. In eight cases mutations involved only the Gla-domain, both at the homozygous or heterozygous level. In five of these eight cases mutation involved gamma-carboxylglutaminic acid residues whereas another non-gamma-carboxylglutaminic residue was involved in three cases. In the latter cases the mutation was always a Phe31Ser mutation. In the remaining cases the mutation in the Gla-domain was associated with mutations in other areas or domains. In the kindred with mutations only in the Gla-domain, FX activity via the extrinsic system varied from 1 to 10% of normal in homozygotes. In the heterozygous population it varied from 36 to 55%. Similar results were observed via the intrinsic system or in Russell viper venom dependent assays whenever these assays were available. Factor X antigen varied between 16 and 55% of normal in almost all cases. In one case it was reported to be normal. In another case it was reported to be low (2%). The bleeding tendency was usually mild to moderate. It was reported to be severe in the family with an associate homozygous factor VII deficiency, and in another instance, FX Algiers. Altogether the pattern seemed, with a few exceptions, fairly uniform so that a satisfactory genotype-phenotype relation could be inferred for the families with defects only in the Gla-domain. On the contrary, no firm conclusion could be drawn for kindred who showed mutations in the Gla-domain associated with defects in other domains.
Girolami
Antonio
A
University of Padua Medical School, Department of Medical and Surgical Sciences, North Eastern Italy Association for the Study of Coagulation Disorders, Padua, Italy. antonio.girolami@unipd.it
Allemand
Emanuele
E
Scandellari
Raffaella
R
Lombardi
Anna Maria
AM
Girolami
Bruno
B
D000595:Amino Acid Sequence; D000941:Antigens / Q000097:blood / Q000276:immunology; D005170:Factor X / Q000032:analysis / Q000737:chemistry* / Q000235:genetics* / Q000276:immunology; D005171:Factor X Deficiency / Q000150:complications / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D006470:Hemorrhage / Q000209:etiology; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D017354:Point Mutation; D017434:Protein Structure, Tertiary
D000941:Antigens; C010515:factor X antigen; D005170:Factor X