# 227600

FACTOR X DEFICIENCY


Alternative titles; symbols

F10 DEFICIENCY
STUART-PROWER FACTOR DEFICIENCY


Phenotype-Gene Relationships

Location Phenotype Phenotype
MIM number
Inheritance Phenotype
mapping key
Gene/Locus Gene/Locus
MIM number
13q34 Factor X deficiency 227600 AR 3 F10 613872
Clinical Synopsis
 

INHERITANCE
- Autosomal recessive
HEAD & NECK
Nose
- Epistaxis
Mouth
- Bleeding gums
GENITOURINARY
Internal Genitalia (Female)
- Menorrhagia
SKELETAL
- Hemarthrosis
MUSCLE, SOFT TISSUES
- Intramuscular hematomas
- Umbilical cord bleeding
NEUROLOGIC
Central Nervous System
- Intracranial hemorrhage
HEMATOLOGY
- Bleeding diathesis
LABORATORY ABNORMALITIES
- Factor X deficiency
- Prolonged prothrombin and partial thromboplastin times
- Russell's viper venom assay may be prolonged or normal, depending on the genetic defect
MISCELLANEOUS
- Variable severity
- Intermediate levels of factor X in mildly symptomatic heterozygotes
- Incidence of 1 in 500,000 live births
MOLECULAR BASIS
- Caused by mutation in the coagulation factor X gene (F10, 613872.0001).

TEXT

A number sign (#) is used with this entry because factor X deficiency is caused by homozygous or compound heterozygous mutation in the gene encoding coagulation factor X (F10; 613872) on chromosome 13q34.


Description

Factor X deficiency is a rare autosomal recessive bleeding disorder showing variable phenotypic severity. Affected individuals can manifest prolonged nasal and mucosal hemorrhage, menorrhagia, hematuria, and occasionally hemarthrosis. The disorder can be caused either by reduced levels of the factor X protein or by synthesis of a dysfunctional factor X protein (summary by Millar et al., 2000).


Clinical Features

Girolami et al. (1970) described a congenital haemorrhagic condition due to the presence of an abnormal factor X in a large kindred from Friuli, a remote valley in northeastern Italy. Girolami et al. (1971) reported another family from Friuli with a bleeding disorder due to an abnormal factor X. The proposita was a 43-year-old woman with a history of bleeding since early childhood. She had had epistaxis, menorrhagia, bleeding after tooth extractions, gum bleeding, postpartum hemorrhage, posttraumatic hemarthroses, and hematuria. Laboratory studies showed prolonged prothrombin time (PT), prolonged partial thromboplastin time (PTT), and correction with Russell viper venom. Factor X activity was significantly decreased (6 to 9% of normal), but antigen levels were normal; however, an abnormal factor X protein was identified immunologically, indicating a qualitative deficiency. The patient's 2 children and mother had 38 to 48% activity levels, consistent with the heterozygous state.

Sumer et al. (1986) reported a Saudi Arabian infant with severe factor X deficiency who had had 2 intracranial hemorrhages.

De Stefano et al. (1988) reported a 13-year-old girl, born of consanguineous parents, with defective factor X. Laboratory studies showed normal factor X antigen levels, but the protein was severely impaired in activation via the intrinsic pathway (3% of normal) and partially defective in activation via the extrinsic pathway (30-50% of normal). The variant protein, termed factor X Roma, was activated by Russell viper venom. The parents of the proposita showed factor X functional levels compatible with heterozygosity for the abnormality. Millar et al. (2000) determined that the Roma variant results from a T318M substitution (613872.0015) in the F10 gene.

Peyvandi et al. (1998) studied 32 Iranian patients with congenital factor X deficiency. The most frequent symptom was epistaxis, which occurred in 72% of patients, with all degrees of deficiency. Other mucosal hemorrhages (e.g., hematuria, gastrointestinal bleeding) were less frequent and occurred mainly in patients with unmeasurable factor X. Menorrhagia occurred in half of the women of reproductive age. Soft tissue bleeding occurred in two-thirds of the patients; spontaneous hematomas and hemarthroses led to severe arthropathy in 5 patients. Bleeding from the umbilical stump was an unexpected finding in 9 patients. The study demonstrated that the bleeding tendency of factor X deficiency can be severe and correlates with factor levels.

Acquired Factor X Deficiency

Furie et al. (1977) presented evidence that the acquired deficiency of factor X associated with systemic amyloidosis is caused by binding of the factor X protein to amyloid.

Ashrani et al. (2003) described factor X deficiency associated with lupus anticoagulant and a bleeding diathesis. They reported 2 patients in whom severe bleeding developed after a respiratory infection. Both the factor X deficiency and lupus anticoagulant were transient. Deficiency of factor X may be another mechanism whereby patients with antiphospholipid antibodies present with bleeding complications.


Other Features

Endo (1981) observed spontaneously developing hematomyelia with incomplete transverse paralysis in a 17-year-old patient with factor X deficiency.

Pregnancy in women with congenital deficiencies of coagulation factors such as factor X is often associated with adverse fetal outcomes. Recurrent spontaneous abortions, placental abruptions, and premature births are reported. Kumar and Mehta (1994) reviewed the outcome of 4 pregnancies in a patient with factor X deficiency. The first 2 pregnancies resulted in the birth of premature babies at 21 and 25 weeks of gestation, both of whom died in the neonatal period. The patient had been treated with fresh frozen plasma for acute bleeding episodes during these pregnancies. In addition, during the second conception she was given factor IX complex prophylactically during the latter half of her pregnancy. During her next 2 pregnancies, she was treated early in pregnancy with prophylactic replacement of factor X. She delivered healthy babies at 34 and 32 weeks of gestation and both babies thrived.


Inheritance

Factor X deficiency is usually inherited in an autosomal recessive pattern (Cooper et al., 1997).

However, Millar et al. (2000) reported a family manifesting an autosomal dominant pattern of inheritance for factor X deficiency. There were 3 clinically affected members who were heterozygous for a splice site mutation that was predicted to lead to the production of a truncated protein product (613872.0012). Millar et al. (2000) presented a model that accounted for the dominant-negative effect of this lesion.


Cytogenetics

Stoll and Roth (1980) described a girl with a duplication-deficiency syndrome involving chromosomes 4 and 13. The mother had a balanced translocation t(4;13)(q26;q34). The child had partial trisomy of 4q and partial monosomy of 13q. Factor X level was half normal.

Pfeiffer et al. (1982) presented evidence suggesting that factors VII (F7; 613878) and X may be encoded by genes on chromosome 13q34. They found deficiency of the 2 factors in 2 cases with 46,XY,t(13;Y)(q11;q34) including probable deletion of a terminal segment of 13q. A prolonged prothrombin time was found before surgery in the first case, leading to studies of coagulation; neither patient had clinical abnormality of coagulation. In 1 case, factor VII was measured as 42%, 40%, and 45% and factor X as 59%, 44%, and 60% of normal, in 2 different laboratories; in the second case, factor VII was 55% and 54% of normal and factor X was 25% and 62%. These values were normal in all 4 parents.

Scambler and Williamson (1985) studied a female monosomic for 13q34 and deficient in clotting factors VII and X, as well as her brother, who was trisomic for 13q34 and had elevated levels of these factors. These persons suffered the effects of segregation from a reciprocal translocation in the mother involving the tip of chromosome 13 (13q34) and 6q24-6q26. DNA dosage studies with a cloned human factor X gene showed that the low levels of factor X expression were due to absence of one copy of the factor X structural gene.


Molecular Genetics

In a patient with a bleeding disorder due to factor X deficiency, Reddy et al. (1989) identified compound heterozygosity for 2 mutations in the F10 gene (613872.0001 and 613872.0002). The patient had prolonged bleeding after surgery, and laboratory studies showed that factor X activity and antigen were 14% and 36% of normal, respectively. This was the first characterization of factor X deficiency at the molecular level.

Bernardi et al. (1989) found that a patient with factor X deficiency was a genetic compound for 2 mutations affecting the F10 gene: the maternal allele contained a partially deleted gene missing the 3-prime portion coding for the catalytic domain of the factor; the defect on the paternal F10 allele was not determined.

James et al. (1991) demonstrated that factor X Friuli is caused by a homozygous mutation in the F10 gene (P343S; 613872.0004).

Wieland et al. (1991) identified an instance of germline mosaicism for deletion of exons 7 and 8 of factor X. One offspring had this deletion and a different deletion inherited from the mother, i.e., she was a compound heterozygote.

Millar et al. (2000) sequenced the F10 genes of 14 unrelated individuals with factor X deficiency, including 12 familial and 2 sporadic cases, and found a total of 13 novel mutations (see, e.g., 613872.0012-612872.0014). Missense mutations were studied by means of molecular modeling, whereas single basepair substitutions in splice sites and the 5-prime flanking region were examined by in vitro splicing assay and luciferase reporter gene assay, respectively. The deletion allele of a novel 6-nucleotide insertion/deletion polymorphism in the F10 gene promoter region was shown by reporter gene assay to reduce promoter activity by approximately 20%. Variation in the antigen level of heterozygous relatives of probands was found to be significantly higher between families than within families, consistent with the view that the nature of the F10 lesion(s) segregating in a given family is a prime determinant of the laboratory phenotype.

Millar et al. (2000) commented that the complete absence of nonsense mutations in the F10 mutational spectrum is highly unusual. The ratio of nonsense to missense mutations is normally approximately 1 in 4. The observed lack of nonsense mutations was statistically significant. Assuming that the relative rate of single basepair substitutions in the F10 gene is similar to the overall mutational spectrum of human genes, this discrepancy would be explicable only in terms of a reduced relative likelihoods of clinical observation (RCOL; Krawczak et al., 1998) of nonsense versus missense mutations as compared with other genes. The reasons for this reduction were not clear.

Peyvandi et al. (2002) analyzed the phenotype and genotype of 15 Iranian patients with factor X deficiency from 13 unrelated families with a high frequency of consanguinity. Nine different homozygous candidate mutations were identified, of which 8 were novel.


Population Genetics

Factor X deficiency has an estimated prevalence of 1 in 500,000 individuals (summary by Millar et al., 2000).


History

Giangrande (2003) gave an account, with photograph, of Miss Audrey Prower, who was 22 years old when she was admitted to University College Hospital of London in 1956 for investigation of a bleeding tendency prior to a dental extraction (Telfer et al., 1956; Denson, 1957). She had had significant bleeding after 2 previous dental extractions and after tonsillectomy. A brother had died of postoperative bleeding after tonsillectomy when he was 5 years old.

Lewis et al. (1953) described a North Carolina patient seemingly similar to Audrey Prower. Hougie et al. (1957) tracked the patient down and confirmed that the defect was the same. As recounted by Giangrande (2003), Rufus Stuart was a 36-year-old farmer and lay-Baptist preacher, a member of a large and interrelated kindred living in the Blue Ridge Mountains of the northwestern corner of North Carolina and neighboring Virginia. He was born of an aunt-nephew mating. His principal problems had been recurrent epistaxis and significant bruising as well as hemarthrosis. Graham et al. (1957) provided a pedigree and showed that the inheritance pattern of the bleeding disorder was clearly autosomal recessive. Giangrande (2003) provided a photograph of Rufus Stuart with 3 of his physicians, Drs. Hougie, Barrow, and Graham.


REFERENCES

  1. Ashrani, A. A., Aysola, A., Al-Khatib, H., Nichols, W. L., Key, N. S. Lupus anticoagulant associated with transient severe factor X deficiency: a report of two patients presenting with major bleeding complications. Brit. J. Haemat. 121: 639-642, 2003. [PubMed: 12752106, related citations] [Full Text]

  2. Aznar, J. A., Espana, F., Aznar, J., Tascon, A., Jimenez, C. Fletcher factor deficiency: report of a new family. Scand. J. Haemat. 21: 94-98, 1978. [PubMed: 694428, related citations] [Full Text]

  3. Bachmann, F. Familienuntersuchungen beim kongenitalen Stuart-Prower-Factor Mangel. Arch. Klaus Stift. Vererbungsforsch. 33: 27-78, 1958.

  4. Bernardi, F., Marchetti, G., Patracchini, P., Volinia, S., Gemmati, D., Simioni, P., Girolami, A. Partial gene deletion in a family with factor X deficiency. Blood 73: 2123-2127, 1989. [PubMed: 2567188, related citations]

  5. Cooper, D. N., Millar, D. S., Wacey, A., Pemberton, S., Tuddenham, E. G. D. Inherited factor X deficiency: molecular genetics and pathophysiology. Thromb. Haemost. 78: 161-172, 1997. [PubMed: 9198147, related citations]

  6. De Stefano, V., Leone, G., Ferrelli, R., Hassan, H. J., Macioce, G., Bizzi, B. Factor X Roma: a congenital factor X variant defective at different degrees in the intrinsic and the extrinsic activation. Brit. J. Haemat. 69: 387-391, 1988. [PubMed: 3408671, related citations] [Full Text]

  7. Denson, K. W. Electrophoretic studies of the Prower factor; a blood coagulation factor which differs from factor VII. Brit. J. Haemat. 4: 313-325, 1957.

  8. Dodds, W. J. Canine factor X (Stuart-Prower factor) deficiency. J. Lab. Clin. Med. 82: 560-566, 1973. [PubMed: 4755433, related citations]

  9. Endo, Y. Congenital factor X deficiency and incomplete transverse paralysis. JAMA 246: 1708, 1981. [PubMed: 7277652, related citations]

  10. Furie, B., Greene, E., Furie, B. C. Syndrome of acquired factor X deficiency and systemic amyloidosis: in vivo studies of the metabolic fate of factor X. New Eng. J. Med. 297: 81-85, 1977. [PubMed: 865580, related citations] [Full Text]

  11. Furie, B., Voo, L., McAdam, K. P. W. J., Furie, B. C. Mechanism of factor X deficiency in systemic amyloidosis. New Eng. J. Med. 304: 827-830, 1981. [PubMed: 7207512, related citations] [Full Text]

  12. Giangrande, P. L. F. Historical review: six characters in search of an author: the history of the nomenclature of coagulation factors. Brit. J. Haemat. 121: 703-712, 2003. [PubMed: 12780784, related citations] [Full Text]

  13. Girolami, A., Lazzarin, M., Procidano, M., Luzzatto, G. A family with heterozygous factor X Friuli defect outside Friuli. Blut 46: 149-154, 1983. [PubMed: 6824795, related citations] [Full Text]

  14. Girolami, A., Lazzarin, M., Scarpa, R., Brunetti, A. Further studies on the abnormal factor X (factor X Friuli) coagulation disorder: a report of another family. Blood 37: 534-541, 1971. [PubMed: 4995085, related citations]

  15. Girolami, A., Molaro, G., Falomo, R. Factor X Friuli coagulation disorder: the demise of the index patient. Acta Haemat. 54: 120-125, 1975. [PubMed: 808943, related citations] [Full Text]

  16. Girolami, A., Molaro, G., Lazzarin, M., Scarpa, R., Brunetti, A. A 'new' congenital haemorrhagic condition due to the presence of an abnormal factor X (factor X Friuli): study of a large kindred. Brit. J. Haemat. 19: 179-192, 1970. [PubMed: 4989292, related citations] [Full Text]

  17. Girolami, A., Molaro, G., Lazzarin, M., Scarpa, R., Brunetti, A. Congenital haemorrhagic condition similar but not identical to factor X deficiency: a haemorrhagic state due to an abnormal factor X? Scand. J. Haemat. 7: 91-99, 1970. [PubMed: 5450692, related citations] [Full Text]

  18. Girolami, A., Nicolini, R., Furlani, E., Bareggi, G. Abnormal factor X (factor X Friuli) coagulation disorder. Acta Haemat. 49: 114-122, 1973. [PubMed: 4196477, related citations] [Full Text]

  19. Girolami, A., Vicarioto, M., Ruzza, G., Cappellato, G., Vergolani, A. Factor X Padua: a 'new' congenital factor X abnormality with a defect only in the extrinsic system. Acta Haemat. 73: 31-36, 1985. [PubMed: 3923765, related citations] [Full Text]

  20. Graham, J. B., Barrow, E. M., Hougie, C. Stuart clotting defect. II. Genetic aspects of a 'new' hemorrhagic state. J. Clin. Invest. 36: 497-503, 1957. [PubMed: 13406064, related citations] [Full Text]

  21. Greipp, P. R., Kyle, R. A., Bowie, E. J. W. Factor X deficiency in primary amyloidosis: resolution after splenectomy. New Eng. J. Med. 301: 1050-1051, 1979. [PubMed: 492235, related citations] [Full Text]

  22. Hougie, C., Barrow, E. M., Graham, J. B. Stuart clotting defect. I. Segregation of an hereditary hemorrhagic state from the heterogeneous group heretofore called 'stable factor' (SPCA, proconvertin, factor VII) deficiency. J. Clin. Invest. 36: 485-496, 1957. [PubMed: 13406063, related citations] [Full Text]

  23. James, H. L., Girolami, A., Fair, D. S. Molecular defect in coagulation factor X(Friuli) results from a substitution of serine for proline at position 343. Blood 77: 317-323, 1991. [PubMed: 1985698, related citations]

  24. Kim, D. J., Thompson, A. R., James, H. L. Factor X(Ketchikan): a variant molecule in which gly replaces a gla residue at position 14 in the light chain. Hum. Genet. 95: 212-214, 1995. [PubMed: 7860069, related citations] [Full Text]

  25. Krawczak, M., Ball, E. V., Cooper, D. N. Neighboring-nucleotide effects on the rates of germ-line single-base-pair substitution in human genes. Am. J. Hum. Genet. 63: 474-488, 1998. [PubMed: 9683596, related citations] [Full Text]

  26. Kroll, A. J., Alexander, B., Cochios, F., Pechet, L. Hereditary deficiencies of clotting factors VII and X associated with carotid-body tumors. New Eng. J. Med. 270: 6-13, 1964. [PubMed: 14062129, related citations] [Full Text]

  27. Kumar, M., Mehta, P. Congenital coagulopathies and pregnancy: report of four pregnancies in a factor X-deficient woman. Am. J. Hemat. 46: 241-244, 1994. [PubMed: 8192155, related citations] [Full Text]

  28. Lewis, J. H., Fresh, J. W., Ferguson, J. H. Congenital hypoproconvertinemia. Proc. Soc. Exp. Biol. Med. 84: 651-654, 1953. [PubMed: 13134245, related citations] [Full Text]

  29. Marchetti, G., Castaman, G., Pinotti, M., Lunghi, B., di Iasio, M. G., Ruggieri, M., Rodeghiero, F. Molecular bases of CRM(+) factor X deficiency: a frequent mutation (Ser334Pro) in the catalytic domain and a substitution (Glu102Lys) in the second EGF-like domain. Brit. J. Haemat. 90: 910-915, 1995. [PubMed: 7669671, related citations] [Full Text]

  30. Messier, T. L., Wong, C. Y., Bovill, E. G., Long, G. L., Church, W. R. Factor X Stockton: a mild bleeding diathesis associated with an active site mutation in factor X. Blood Coagul. Fibrinolysis 7: 5-14, 1996. [PubMed: 8845463, related citations]

  31. Millar, D. S., Elliston, L., Deex, P., Krawczak, M., Wacey, A. I., Reynaud, J., Nieuwenhuis, H. K., Bolton-Maggs, P., Mannucci, P. M., Reverter, J. C., Cachia, P., Pasi, K. J., Layton, D. M., Cooper, D. N. Molecular analysis of the genotype-phenotype relationship in factor X deficiency. Hum. Genet. 106: 249-257, 2000. [PubMed: 10746568, related citations] [Full Text]

  32. Mori, K., Sakai, H., Nakano, N., Suzuki, S., Sugal, K., Hisa, S., Goto, Y. Congenital factor X deficiency in Japan. Tohoku J. Exp. Med. 133: 1-19, 1981. [PubMed: 7233424, related citations] [Full Text]

  33. Peyvandi, F., Mannucci, P. M., Lak, M., Abdoullahi, M., Zeinali, S., Sharifian, R., Perry, D. Congenital factor X deficiency: spectrum of bleeding symptoms in 32 Iranian patients. Brit. J. Haemat. 102: 626-628, 1998. [PubMed: 9695984, related citations] [Full Text]

  34. Peyvandi, F., Menegatti, M., Santagostino, E., Akhavan, S., Uprichard, J., Perry, D. J., Perkins, S. J., Mannucci, P. M. Gene mutations and three-dimensional structural analysis in 13 families with severe factor X deficiency. Brit. J. Haemat. 117: 685-692, 2002. [PubMed: 12028042, related citations] [Full Text]

  35. Pfeiffer, R. A., Ott, R., Gilgenkrantz, S., Alexandre, P. Deficiency of coagulation factors VII and X associated with deletion of a chromosome 13 (q34): evidence from two cases with 46,XY,t(13;Y)(q11;q34). Hum. Genet. 62: 358-360, 1982. [PubMed: 6985471, related citations] [Full Text]

  36. Racchi, M., Watzke, H. H., High, K. A., Lively, M. O. Human coagulation factor X deficiency caused by a mutant signal peptide that blocks cleavage by signal peptidase but not targeting and translocation to the endoplasmic reticulum. J. Biol. Chem. 268: 5735-5740, 1993. [PubMed: 8449937, related citations]

  37. Reddy, S. V., Zhou, Z.-Q., Rao, K. J., Scott, J. P., Watzke, H., High, K. A., Jagadeeswaran, P. Molecular characterization of human factor X(San Antonio). Blood 74: 1486-1490, 1989. [PubMed: 2790181, related citations]

  38. Roos, J., Huizinga, J. Genetic investigation of the Stuart coagulation defect. Acta Genet. Statist. Med. 9: 115-122, 1959.

  39. Scambler, P. J., Williamson, R. The structural gene for human coagulation factor X is located on chromosome 13q34. Cytogenet. Cell Genet. 39: 231-233, 1985. [PubMed: 4042693, related citations] [Full Text]

  40. Stoll, C., Roth, M. P. Partial 4q duplication due to inherited der(13), t(4;13)(q26;q34)mat in a girl with a deficiency of factor X. Hum. Genet. 53: 303-304, 1980. [PubMed: 6985462, related citations] [Full Text]

  41. Sumer, T., Ahmad, M., Sumer, N. K., Al-Mouzan, M. I. Severe congenital factor X deficiency with intracranial haemorrhage. Europ. J. Pediat. 145: 119-120, 1986. [PubMed: 3732313, related citations] [Full Text]

  42. Telfer, T. P., Denson, K. W., Wright, D. R. A 'new' coagulation defect. Brit. J. Haemat. 2: 308-316, 1956. [PubMed: 13342365, related citations] [Full Text]

  43. Watzke, H. H., Lechner, K., Roberts, H. R., Reddy, S. V., Welsch, D. J., Friedman, P., Mahr, G., Jagadeeswaran, P., Monroe, D. M., High, K. A. Molecular defect (gla(+14)-to-lys) and its functional consequences in a hereditary factor X deficiency (factor X 'Vorarlberg'). J. Biol. Chem. 265: 11982-11989, 1990. [PubMed: 1973167, related citations]

  44. Watzke, H. H., Wallmark, A., Hamaguchi, N., Giardina, P., Stafford, D. W., High, K. A. Factor X (Santo Domingo): evidence that the severe clinical phenotype arises from a mutation blocking secretion. J. Clin. Invest. 88: 1685-1689, 1991. [PubMed: 1939653, related citations] [Full Text]

  45. Wieland, K., Millar, D. S., Grundy, C. B., Mibashan, R. S., Kakkar, V. V., Cooper, D. N. Molecular genetic analysis of factor X deficiency: gene deletion and germline mosaicism. Hum. Genet. 86: 273-278, 1991. [PubMed: 1997381, related citations] [Full Text]


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# 227600

FACTOR X DEFICIENCY


Alternative titles; symbols

F10 DEFICIENCY
STUART-PROWER FACTOR DEFICIENCY


SNOMEDCT: 76642003;   ORPHA: 328;   DO: 2222;  


Phenotype-Gene Relationships

Location Phenotype Phenotype
MIM number
Inheritance Phenotype
mapping key
Gene/Locus Gene/Locus
MIM number
13q34 Factor X deficiency 227600 Autosomal recessive 3 F10 613872

TEXT

A number sign (#) is used with this entry because factor X deficiency is caused by homozygous or compound heterozygous mutation in the gene encoding coagulation factor X (F10; 613872) on chromosome 13q34.


Description

Factor X deficiency is a rare autosomal recessive bleeding disorder showing variable phenotypic severity. Affected individuals can manifest prolonged nasal and mucosal hemorrhage, menorrhagia, hematuria, and occasionally hemarthrosis. The disorder can be caused either by reduced levels of the factor X protein or by synthesis of a dysfunctional factor X protein (summary by Millar et al., 2000).


Clinical Features

Girolami et al. (1970) described a congenital haemorrhagic condition due to the presence of an abnormal factor X in a large kindred from Friuli, a remote valley in northeastern Italy. Girolami et al. (1971) reported another family from Friuli with a bleeding disorder due to an abnormal factor X. The proposita was a 43-year-old woman with a history of bleeding since early childhood. She had had epistaxis, menorrhagia, bleeding after tooth extractions, gum bleeding, postpartum hemorrhage, posttraumatic hemarthroses, and hematuria. Laboratory studies showed prolonged prothrombin time (PT), prolonged partial thromboplastin time (PTT), and correction with Russell viper venom. Factor X activity was significantly decreased (6 to 9% of normal), but antigen levels were normal; however, an abnormal factor X protein was identified immunologically, indicating a qualitative deficiency. The patient's 2 children and mother had 38 to 48% activity levels, consistent with the heterozygous state.

Sumer et al. (1986) reported a Saudi Arabian infant with severe factor X deficiency who had had 2 intracranial hemorrhages.

De Stefano et al. (1988) reported a 13-year-old girl, born of consanguineous parents, with defective factor X. Laboratory studies showed normal factor X antigen levels, but the protein was severely impaired in activation via the intrinsic pathway (3% of normal) and partially defective in activation via the extrinsic pathway (30-50% of normal). The variant protein, termed factor X Roma, was activated by Russell viper venom. The parents of the proposita showed factor X functional levels compatible with heterozygosity for the abnormality. Millar et al. (2000) determined that the Roma variant results from a T318M substitution (613872.0015) in the F10 gene.

Peyvandi et al. (1998) studied 32 Iranian patients with congenital factor X deficiency. The most frequent symptom was epistaxis, which occurred in 72% of patients, with all degrees of deficiency. Other mucosal hemorrhages (e.g., hematuria, gastrointestinal bleeding) were less frequent and occurred mainly in patients with unmeasurable factor X. Menorrhagia occurred in half of the women of reproductive age. Soft tissue bleeding occurred in two-thirds of the patients; spontaneous hematomas and hemarthroses led to severe arthropathy in 5 patients. Bleeding from the umbilical stump was an unexpected finding in 9 patients. The study demonstrated that the bleeding tendency of factor X deficiency can be severe and correlates with factor levels.

Acquired Factor X Deficiency

Furie et al. (1977) presented evidence that the acquired deficiency of factor X associated with systemic amyloidosis is caused by binding of the factor X protein to amyloid.

Ashrani et al. (2003) described factor X deficiency associated with lupus anticoagulant and a bleeding diathesis. They reported 2 patients in whom severe bleeding developed after a respiratory infection. Both the factor X deficiency and lupus anticoagulant were transient. Deficiency of factor X may be another mechanism whereby patients with antiphospholipid antibodies present with bleeding complications.


Other Features

Endo (1981) observed spontaneously developing hematomyelia with incomplete transverse paralysis in a 17-year-old patient with factor X deficiency.

Pregnancy in women with congenital deficiencies of coagulation factors such as factor X is often associated with adverse fetal outcomes. Recurrent spontaneous abortions, placental abruptions, and premature births are reported. Kumar and Mehta (1994) reviewed the outcome of 4 pregnancies in a patient with factor X deficiency. The first 2 pregnancies resulted in the birth of premature babies at 21 and 25 weeks of gestation, both of whom died in the neonatal period. The patient had been treated with fresh frozen plasma for acute bleeding episodes during these pregnancies. In addition, during the second conception she was given factor IX complex prophylactically during the latter half of her pregnancy. During her next 2 pregnancies, she was treated early in pregnancy with prophylactic replacement of factor X. She delivered healthy babies at 34 and 32 weeks of gestation and both babies thrived.


Inheritance

Factor X deficiency is usually inherited in an autosomal recessive pattern (Cooper et al., 1997).

However, Millar et al. (2000) reported a family manifesting an autosomal dominant pattern of inheritance for factor X deficiency. There were 3 clinically affected members who were heterozygous for a splice site mutation that was predicted to lead to the production of a truncated protein product (613872.0012). Millar et al. (2000) presented a model that accounted for the dominant-negative effect of this lesion.


Cytogenetics

Stoll and Roth (1980) described a girl with a duplication-deficiency syndrome involving chromosomes 4 and 13. The mother had a balanced translocation t(4;13)(q26;q34). The child had partial trisomy of 4q and partial monosomy of 13q. Factor X level was half normal.

Pfeiffer et al. (1982) presented evidence suggesting that factors VII (F7; 613878) and X may be encoded by genes on chromosome 13q34. They found deficiency of the 2 factors in 2 cases with 46,XY,t(13;Y)(q11;q34) including probable deletion of a terminal segment of 13q. A prolonged prothrombin time was found before surgery in the first case, leading to studies of coagulation; neither patient had clinical abnormality of coagulation. In 1 case, factor VII was measured as 42%, 40%, and 45% and factor X as 59%, 44%, and 60% of normal, in 2 different laboratories; in the second case, factor VII was 55% and 54% of normal and factor X was 25% and 62%. These values were normal in all 4 parents.

Scambler and Williamson (1985) studied a female monosomic for 13q34 and deficient in clotting factors VII and X, as well as her brother, who was trisomic for 13q34 and had elevated levels of these factors. These persons suffered the effects of segregation from a reciprocal translocation in the mother involving the tip of chromosome 13 (13q34) and 6q24-6q26. DNA dosage studies with a cloned human factor X gene showed that the low levels of factor X expression were due to absence of one copy of the factor X structural gene.


Molecular Genetics

In a patient with a bleeding disorder due to factor X deficiency, Reddy et al. (1989) identified compound heterozygosity for 2 mutations in the F10 gene (613872.0001 and 613872.0002). The patient had prolonged bleeding after surgery, and laboratory studies showed that factor X activity and antigen were 14% and 36% of normal, respectively. This was the first characterization of factor X deficiency at the molecular level.

Bernardi et al. (1989) found that a patient with factor X deficiency was a genetic compound for 2 mutations affecting the F10 gene: the maternal allele contained a partially deleted gene missing the 3-prime portion coding for the catalytic domain of the factor; the defect on the paternal F10 allele was not determined.

James et al. (1991) demonstrated that factor X Friuli is caused by a homozygous mutation in the F10 gene (P343S; 613872.0004).

Wieland et al. (1991) identified an instance of germline mosaicism for deletion of exons 7 and 8 of factor X. One offspring had this deletion and a different deletion inherited from the mother, i.e., she was a compound heterozygote.

Millar et al. (2000) sequenced the F10 genes of 14 unrelated individuals with factor X deficiency, including 12 familial and 2 sporadic cases, and found a total of 13 novel mutations (see, e.g., 613872.0012-612872.0014). Missense mutations were studied by means of molecular modeling, whereas single basepair substitutions in splice sites and the 5-prime flanking region were examined by in vitro splicing assay and luciferase reporter gene assay, respectively. The deletion allele of a novel 6-nucleotide insertion/deletion polymorphism in the F10 gene promoter region was shown by reporter gene assay to reduce promoter activity by approximately 20%. Variation in the antigen level of heterozygous relatives of probands was found to be significantly higher between families than within families, consistent with the view that the nature of the F10 lesion(s) segregating in a given family is a prime determinant of the laboratory phenotype.

Millar et al. (2000) commented that the complete absence of nonsense mutations in the F10 mutational spectrum is highly unusual. The ratio of nonsense to missense mutations is normally approximately 1 in 4. The observed lack of nonsense mutations was statistically significant. Assuming that the relative rate of single basepair substitutions in the F10 gene is similar to the overall mutational spectrum of human genes, this discrepancy would be explicable only in terms of a reduced relative likelihoods of clinical observation (RCOL; Krawczak et al., 1998) of nonsense versus missense mutations as compared with other genes. The reasons for this reduction were not clear.

Peyvandi et al. (2002) analyzed the phenotype and genotype of 15 Iranian patients with factor X deficiency from 13 unrelated families with a high frequency of consanguinity. Nine different homozygous candidate mutations were identified, of which 8 were novel.


Population Genetics

Factor X deficiency has an estimated prevalence of 1 in 500,000 individuals (summary by Millar et al., 2000).


History

Giangrande (2003) gave an account, with photograph, of Miss Audrey Prower, who was 22 years old when she was admitted to University College Hospital of London in 1956 for investigation of a bleeding tendency prior to a dental extraction (Telfer et al., 1956; Denson, 1957). She had had significant bleeding after 2 previous dental extractions and after tonsillectomy. A brother had died of postoperative bleeding after tonsillectomy when he was 5 years old.

Lewis et al. (1953) described a North Carolina patient seemingly similar to Audrey Prower. Hougie et al. (1957) tracked the patient down and confirmed that the defect was the same. As recounted by Giangrande (2003), Rufus Stuart was a 36-year-old farmer and lay-Baptist preacher, a member of a large and interrelated kindred living in the Blue Ridge Mountains of the northwestern corner of North Carolina and neighboring Virginia. He was born of an aunt-nephew mating. His principal problems had been recurrent epistaxis and significant bruising as well as hemarthrosis. Graham et al. (1957) provided a pedigree and showed that the inheritance pattern of the bleeding disorder was clearly autosomal recessive. Giangrande (2003) provided a photograph of Rufus Stuart with 3 of his physicians, Drs. Hougie, Barrow, and Graham.


See Also:

Aznar et al. (1978); Bachmann (1958); Dodds (1973); Furie et al. (1981); Girolami et al. (1983); Girolami et al. (1975); Girolami et al. (1970); Girolami et al. (1973); Girolami et al. (1985); Greipp et al. (1979); Kim et al. (1995); Kroll et al. (1964); Marchetti et al. (1995); Messier et al. (1996); Mori et al. (1981); Racchi et al. (1993); Roos and Huizinga (1959); Watzke et al. (1990); Watzke et al. (1991)

REFERENCES

  1. Ashrani, A. A., Aysola, A., Al-Khatib, H., Nichols, W. L., Key, N. S. Lupus anticoagulant associated with transient severe factor X deficiency: a report of two patients presenting with major bleeding complications. Brit. J. Haemat. 121: 639-642, 2003. [PubMed: 12752106] [Full Text: https://doi.org/10.1046/j.1365-2141.2003.04325.x]

  2. Aznar, J. A., Espana, F., Aznar, J., Tascon, A., Jimenez, C. Fletcher factor deficiency: report of a new family. Scand. J. Haemat. 21: 94-98, 1978. [PubMed: 694428] [Full Text: https://doi.org/10.1111/j.1600-0609.1978.tb02498.x]

  3. Bachmann, F. Familienuntersuchungen beim kongenitalen Stuart-Prower-Factor Mangel. Arch. Klaus Stift. Vererbungsforsch. 33: 27-78, 1958.

  4. Bernardi, F., Marchetti, G., Patracchini, P., Volinia, S., Gemmati, D., Simioni, P., Girolami, A. Partial gene deletion in a family with factor X deficiency. Blood 73: 2123-2127, 1989. [PubMed: 2567188]

  5. Cooper, D. N., Millar, D. S., Wacey, A., Pemberton, S., Tuddenham, E. G. D. Inherited factor X deficiency: molecular genetics and pathophysiology. Thromb. Haemost. 78: 161-172, 1997. [PubMed: 9198147]

  6. De Stefano, V., Leone, G., Ferrelli, R., Hassan, H. J., Macioce, G., Bizzi, B. Factor X Roma: a congenital factor X variant defective at different degrees in the intrinsic and the extrinsic activation. Brit. J. Haemat. 69: 387-391, 1988. [PubMed: 3408671] [Full Text: https://doi.org/10.1111/j.1365-2141.1988.tb02378.x]

  7. Denson, K. W. Electrophoretic studies of the Prower factor; a blood coagulation factor which differs from factor VII. Brit. J. Haemat. 4: 313-325, 1957.

  8. Dodds, W. J. Canine factor X (Stuart-Prower factor) deficiency. J. Lab. Clin. Med. 82: 560-566, 1973. [PubMed: 4755433]

  9. Endo, Y. Congenital factor X deficiency and incomplete transverse paralysis. JAMA 246: 1708, 1981. [PubMed: 7277652]

  10. Furie, B., Greene, E., Furie, B. C. Syndrome of acquired factor X deficiency and systemic amyloidosis: in vivo studies of the metabolic fate of factor X. New Eng. J. Med. 297: 81-85, 1977. [PubMed: 865580] [Full Text: https://doi.org/10.1056/NEJM197707142970203]

  11. Furie, B., Voo, L., McAdam, K. P. W. J., Furie, B. C. Mechanism of factor X deficiency in systemic amyloidosis. New Eng. J. Med. 304: 827-830, 1981. [PubMed: 7207512] [Full Text: https://doi.org/10.1056/NEJM198104023041407]

  12. Giangrande, P. L. F. Historical review: six characters in search of an author: the history of the nomenclature of coagulation factors. Brit. J. Haemat. 121: 703-712, 2003. [PubMed: 12780784] [Full Text: https://doi.org/10.1046/j.1365-2141.2003.04333.x]

  13. Girolami, A., Lazzarin, M., Procidano, M., Luzzatto, G. A family with heterozygous factor X Friuli defect outside Friuli. Blut 46: 149-154, 1983. [PubMed: 6824795] [Full Text: https://doi.org/10.1007/BF00320273]

  14. Girolami, A., Lazzarin, M., Scarpa, R., Brunetti, A. Further studies on the abnormal factor X (factor X Friuli) coagulation disorder: a report of another family. Blood 37: 534-541, 1971. [PubMed: 4995085]

  15. Girolami, A., Molaro, G., Falomo, R. Factor X Friuli coagulation disorder: the demise of the index patient. Acta Haemat. 54: 120-125, 1975. [PubMed: 808943] [Full Text: https://doi.org/10.1159/000208061]

  16. Girolami, A., Molaro, G., Lazzarin, M., Scarpa, R., Brunetti, A. A 'new' congenital haemorrhagic condition due to the presence of an abnormal factor X (factor X Friuli): study of a large kindred. Brit. J. Haemat. 19: 179-192, 1970. [PubMed: 4989292] [Full Text: https://doi.org/10.1111/j.1365-2141.1970.tb01615.x]

  17. Girolami, A., Molaro, G., Lazzarin, M., Scarpa, R., Brunetti, A. Congenital haemorrhagic condition similar but not identical to factor X deficiency: a haemorrhagic state due to an abnormal factor X? Scand. J. Haemat. 7: 91-99, 1970. [PubMed: 5450692] [Full Text: https://doi.org/10.1111/j.1600-0609.1970.tb01874.x]

  18. Girolami, A., Nicolini, R., Furlani, E., Bareggi, G. Abnormal factor X (factor X Friuli) coagulation disorder. Acta Haemat. 49: 114-122, 1973. [PubMed: 4196477] [Full Text: https://doi.org/10.1159/000208392]

  19. Girolami, A., Vicarioto, M., Ruzza, G., Cappellato, G., Vergolani, A. Factor X Padua: a 'new' congenital factor X abnormality with a defect only in the extrinsic system. Acta Haemat. 73: 31-36, 1985. [PubMed: 3923765] [Full Text: https://doi.org/10.1159/000206269]

  20. Graham, J. B., Barrow, E. M., Hougie, C. Stuart clotting defect. II. Genetic aspects of a 'new' hemorrhagic state. J. Clin. Invest. 36: 497-503, 1957. [PubMed: 13406064] [Full Text: https://doi.org/10.1172/JCI103447]

  21. Greipp, P. R., Kyle, R. A., Bowie, E. J. W. Factor X deficiency in primary amyloidosis: resolution after splenectomy. New Eng. J. Med. 301: 1050-1051, 1979. [PubMed: 492235] [Full Text: https://doi.org/10.1056/NEJM197911083011907]

  22. Hougie, C., Barrow, E. M., Graham, J. B. Stuart clotting defect. I. Segregation of an hereditary hemorrhagic state from the heterogeneous group heretofore called 'stable factor' (SPCA, proconvertin, factor VII) deficiency. J. Clin. Invest. 36: 485-496, 1957. [PubMed: 13406063] [Full Text: https://doi.org/10.1172/JCI103446]

  23. James, H. L., Girolami, A., Fair, D. S. Molecular defect in coagulation factor X(Friuli) results from a substitution of serine for proline at position 343. Blood 77: 317-323, 1991. [PubMed: 1985698]

  24. Kim, D. J., Thompson, A. R., James, H. L. Factor X(Ketchikan): a variant molecule in which gly replaces a gla residue at position 14 in the light chain. Hum. Genet. 95: 212-214, 1995. [PubMed: 7860069] [Full Text: https://doi.org/10.1007/BF00209404]

  25. Krawczak, M., Ball, E. V., Cooper, D. N. Neighboring-nucleotide effects on the rates of germ-line single-base-pair substitution in human genes. Am. J. Hum. Genet. 63: 474-488, 1998. [PubMed: 9683596] [Full Text: https://doi.org/10.1086/301965]

  26. Kroll, A. J., Alexander, B., Cochios, F., Pechet, L. Hereditary deficiencies of clotting factors VII and X associated with carotid-body tumors. New Eng. J. Med. 270: 6-13, 1964. [PubMed: 14062129] [Full Text: https://doi.org/10.1056/NEJM196401022700102]

  27. Kumar, M., Mehta, P. Congenital coagulopathies and pregnancy: report of four pregnancies in a factor X-deficient woman. Am. J. Hemat. 46: 241-244, 1994. [PubMed: 8192155] [Full Text: https://doi.org/10.1002/ajh.2830460315]

  28. Lewis, J. H., Fresh, J. W., Ferguson, J. H. Congenital hypoproconvertinemia. Proc. Soc. Exp. Biol. Med. 84: 651-654, 1953. [PubMed: 13134245] [Full Text: https://doi.org/10.3181/00379727-84-20741]

  29. Marchetti, G., Castaman, G., Pinotti, M., Lunghi, B., di Iasio, M. G., Ruggieri, M., Rodeghiero, F. Molecular bases of CRM(+) factor X deficiency: a frequent mutation (Ser334Pro) in the catalytic domain and a substitution (Glu102Lys) in the second EGF-like domain. Brit. J. Haemat. 90: 910-915, 1995. [PubMed: 7669671] [Full Text: https://doi.org/10.1111/j.1365-2141.1995.tb05214.x]

  30. Messier, T. L., Wong, C. Y., Bovill, E. G., Long, G. L., Church, W. R. Factor X Stockton: a mild bleeding diathesis associated with an active site mutation in factor X. Blood Coagul. Fibrinolysis 7: 5-14, 1996. [PubMed: 8845463]

  31. Millar, D. S., Elliston, L., Deex, P., Krawczak, M., Wacey, A. I., Reynaud, J., Nieuwenhuis, H. K., Bolton-Maggs, P., Mannucci, P. M., Reverter, J. C., Cachia, P., Pasi, K. J., Layton, D. M., Cooper, D. N. Molecular analysis of the genotype-phenotype relationship in factor X deficiency. Hum. Genet. 106: 249-257, 2000. [PubMed: 10746568] [Full Text: https://doi.org/10.1007/s004390051035]

  32. Mori, K., Sakai, H., Nakano, N., Suzuki, S., Sugal, K., Hisa, S., Goto, Y. Congenital factor X deficiency in Japan. Tohoku J. Exp. Med. 133: 1-19, 1981. [PubMed: 7233424] [Full Text: https://doi.org/10.1620/tjem.133.1]

  33. Peyvandi, F., Mannucci, P. M., Lak, M., Abdoullahi, M., Zeinali, S., Sharifian, R., Perry, D. Congenital factor X deficiency: spectrum of bleeding symptoms in 32 Iranian patients. Brit. J. Haemat. 102: 626-628, 1998. [PubMed: 9695984] [Full Text: https://doi.org/10.1046/j.1365-2141.1998.00806.x]

  34. Peyvandi, F., Menegatti, M., Santagostino, E., Akhavan, S., Uprichard, J., Perry, D. J., Perkins, S. J., Mannucci, P. M. Gene mutations and three-dimensional structural analysis in 13 families with severe factor X deficiency. Brit. J. Haemat. 117: 685-692, 2002. [PubMed: 12028042] [Full Text: https://doi.org/10.1046/j.1365-2141.2002.03486.x]

  35. Pfeiffer, R. A., Ott, R., Gilgenkrantz, S., Alexandre, P. Deficiency of coagulation factors VII and X associated with deletion of a chromosome 13 (q34): evidence from two cases with 46,XY,t(13;Y)(q11;q34). Hum. Genet. 62: 358-360, 1982. [PubMed: 6985471] [Full Text: https://doi.org/10.1007/BF00304557]

  36. Racchi, M., Watzke, H. H., High, K. A., Lively, M. O. Human coagulation factor X deficiency caused by a mutant signal peptide that blocks cleavage by signal peptidase but not targeting and translocation to the endoplasmic reticulum. J. Biol. Chem. 268: 5735-5740, 1993. [PubMed: 8449937]

  37. Reddy, S. V., Zhou, Z.-Q., Rao, K. J., Scott, J. P., Watzke, H., High, K. A., Jagadeeswaran, P. Molecular characterization of human factor X(San Antonio). Blood 74: 1486-1490, 1989. [PubMed: 2790181]

  38. Roos, J., Huizinga, J. Genetic investigation of the Stuart coagulation defect. Acta Genet. Statist. Med. 9: 115-122, 1959.

  39. Scambler, P. J., Williamson, R. The structural gene for human coagulation factor X is located on chromosome 13q34. Cytogenet. Cell Genet. 39: 231-233, 1985. [PubMed: 4042693] [Full Text: https://doi.org/10.1159/000132141]

  40. Stoll, C., Roth, M. P. Partial 4q duplication due to inherited der(13), t(4;13)(q26;q34)mat in a girl with a deficiency of factor X. Hum. Genet. 53: 303-304, 1980. [PubMed: 6985462] [Full Text: https://doi.org/10.1007/BF00287045]

  41. Sumer, T., Ahmad, M., Sumer, N. K., Al-Mouzan, M. I. Severe congenital factor X deficiency with intracranial haemorrhage. Europ. J. Pediat. 145: 119-120, 1986. [PubMed: 3732313] [Full Text: https://doi.org/10.1007/BF00441870]

  42. Telfer, T. P., Denson, K. W., Wright, D. R. A 'new' coagulation defect. Brit. J. Haemat. 2: 308-316, 1956. [PubMed: 13342365] [Full Text: https://doi.org/10.1111/j.1365-2141.1956.tb06703.x]

  43. Watzke, H. H., Lechner, K., Roberts, H. R., Reddy, S. V., Welsch, D. J., Friedman, P., Mahr, G., Jagadeeswaran, P., Monroe, D. M., High, K. A. Molecular defect (gla(+14)-to-lys) and its functional consequences in a hereditary factor X deficiency (factor X 'Vorarlberg'). J. Biol. Chem. 265: 11982-11989, 1990. [PubMed: 1973167]

  44. Watzke, H. H., Wallmark, A., Hamaguchi, N., Giardina, P., Stafford, D. W., High, K. A. Factor X (Santo Domingo): evidence that the severe clinical phenotype arises from a mutation blocking secretion. J. Clin. Invest. 88: 1685-1689, 1991. [PubMed: 1939653] [Full Text: https://doi.org/10.1172/JCI115484]

  45. Wieland, K., Millar, D. S., Grundy, C. B., Mibashan, R. S., Kakkar, V. V., Cooper, D. N. Molecular genetic analysis of factor X deficiency: gene deletion and germline mosaicism. Hum. Genet. 86: 273-278, 1991. [PubMed: 1997381] [Full Text: https://doi.org/10.1007/BF00202408]


Contributors:
Cassandra L. Kniffin - reorganized : 4/8/2011
Cassandra L. Kniffin - updated : 4/7/2011
Victor A. McKusick - updated : 10/4/2004
Victor A. McKusick - updated : 9/8/2003
Victor A. McKusick - updated : 9/4/2003
Victor A. McKusick - updated : 9/13/2002
Victor A. McKusick - updated : 8/1/2001
Victor A. McKusick - updated : 3/8/2000
Victor A. McKusick - updated : 1/14/2000
Victor A. McKusick - updated : 3/10/1999
Lori M. Kelman - updated : 8/25/1997
Victor A. McKusick - updated : 8/27/1997

Creation Date:
Victor A. McKusick : 6/3/1986

Edit History:
alopez : 05/22/2017
carol : 06/01/2016
alopez : 8/11/2015
carol : 4/11/2011
carol : 4/8/2011
ckniffin : 4/7/2011
ckniffin : 4/7/2011
terry : 5/19/2010
carol : 12/16/2009
terry : 6/3/2009
carol : 10/21/2008
carol : 10/9/2008
wwang : 2/15/2007
terry : 3/22/2006
tkritzer : 10/7/2004
terry : 10/4/2004
alopez : 3/17/2004
cwells : 9/30/2003
terry : 9/8/2003
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carol : 9/18/2002
tkritzer : 9/13/2002
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carol : 8/16/2001
mcapotos : 8/6/2001
terry : 8/1/2001
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mcapotos : 2/1/2000
terry : 1/14/2000
kayiaros : 7/8/1999
terry : 6/11/1999
terry : 3/10/1999
psherman : 1/8/1999
dkim : 12/16/1998
dholmes : 11/11/1997
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jenny : 9/5/1997
terry : 8/27/1997
dholmes : 8/25/1997
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alopez : 8/8/1997
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mark : 4/28/1996
terry : 4/22/1996
mark : 2/9/1996
terry : 1/30/1996
mark : 5/11/1995
terry : 8/25/1994
mimadm : 2/19/1994
carol : 5/26/1993
carol : 5/14/1993
supermim : 3/16/1992