A new factor X defect (factor X Padua 3): a compound heterozygous between true deficiency (Gly(380)-->Arg) and an abnormality (Ser(334)-->Pro).
We report a novel mutation in Factor X (FX) gene which results in a phenotype without any bleeding tendency. The proband has been found to be a compound heterozygote between a novel FX true deficiency (Gly(380)-->Arg) and a previously reported dysfunctional mutation Ser(334)-->Pro (FX Marsiglia). Prothrombin time (PT) and partial thromboplastin time (PTT) were moderately prolonged and were fully corrected by the addition of normal serum. Her FX activity level varied between 8% and 19% of normal according to the method used whereas the FX antigen level was 40% of the normal control value. All the exons and intron/exon junctions of the FX gene were studied using a combined approach of polymerase chain reaction and conformation sensitive gel electrophoresis. A transversion G to A in exon 8 resulting in the replacement of Gly380 by Arg was found in the proband, in the father and in a proband's brother, whereas heterozygous FX Marsiglia was present in the proband's mother and her sister. Gly380 is strictly linked to Ser379, a component of the catalytic triad. The substitution of Gly for Arg causes the introduction of a large charged amino acid which could affect the catalytic function of FX leading to secretion problem, accounting for the cross-reactive material (CRM) negative phenotype.
Vianello
F
F
Department of Medical and Surgical Sciences, Second Chair of Medicine, University of Padua, via Ospedale 105, 35100 Padua, Italy.
Lombardi
A M
AM
Boldrin
C
C
Luni
S
S
Girolami
A
A
D000328:Adult; D000941:Antigens / Q000032:analysis; D004252:DNA Mutational Analysis; D005170:Factor X / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D005171:Factor X Deficiency / Q000235:genetics*; D005192:Family Health; D005260:Female; D006579:Heterozygote; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010314:Partial Thromboplastin Time; D010375:Pedigree; D010641:Phenotype
D000941:Antigens; D005170:Factor X