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Detection of christmas disease (hemophilia b) carriers ^*

N. Ferrari^I; C.R. Rizza^II

^IDepartamento de Biologia, Universidade Federal de Santa Catarina, 88090 Florianópolis, SC, Brasil. Send correspondence to N.F.
^IIOxford Haemophilia Centre, Churchill Hospital, Oxford, OX3 7LJ, England

ABSTRACT

Factor IX (FIX) is a plasma glycoprotein which participates in the blood coagulation process. Congenital deficiency of FIX causes Christmas disease, an X-linked recessive disorder. Factor IX clotting activity (FIXc) and factor IX antigen (FIXAg) levels were measured in the plasmas of 26 unrelated healthy females and in 61 obligatory carriers of Christmas disease. The results os these measurements were used in a discriminant analysis and a formula was obtained to calculate probability of carriership, to be used for possible carriers. FIXc levels, FIXAg levels, age and the information obtained from pedigre analysis were all shown to be important in carrier detection.

Keywords: christmas disease; hemophilia b.

REFERENCES

Aggeler, A.M., White, S.G., Glendening, M.B., Page, E.W., Leake, T.B. and Bates, G. (1952). Plasma thromboplastin component (PTC) deficiency: a new disease resembling classical haemophilia. Proc. Soc. Exp. Biol. Med. 79:692-694.

Armitage, P. (1971). Statistical Methods in Medical Research. Blackwell Scientific Publications, Oxford.

Austen, D.E.G. and Rhymes, I.R. (1975). A Laboratory Manual of Blood Coagulation. Blackwell Scientific Publications, Oxford.

Barrow, E.M., Bullock, W.R. and Graham, J.B. (1960). A study of the carrier state for plasma thromboplastin component (P.T.C. Christmas factor) deficiency utilizing a new assay procedure. J. Lab. Clin. Med. 55: 936-945.

Biggs, R., Douglas, A.S., MacFarlane, R.G., Dacie, J.V., Pitney, W.R. and Merskey, C. (1952). Christmas disease: a condition previously mistaken for haemophilia. Br. Med. J. ii: 1378-1388.

Denson, K.W.E., Biggs, R. and Mannucci, P.N. (1968). An investigation of three patients with Christmas disease due to an abnormal type of factor IX. J. Clin. Pathol. 21: 160-165.

Frota- Pessoa, O., Gomes, E.L. and Calicohio, T.R. (1963). Dosage compensation and the production of blood coagulation factor IX. Science 139: 348-349.

Giannelli, C., Choo, K.H., Winship, P.R., Rizza, C.R., Anson, D.S., Rees, D.J.G., Ferrari, N. and

Brownlee, G.G. (1984). Characterization and use of an intergenic polymorphic marker for detection of carriers of haemophilia B (factor IX deficiency). Lancet 8371(1): 239-241.

Graham, J.B., Flyer, P., Elston, R.C. and Kasper, C.K. (1979). Statistical study of genotype assignment (carrier detection) in haemophilia B. Thromb. Res. 15:69-78.

Grunebaum, L., Cazenave, J.P., Camerino, G., Kloepter, C., Mandel, J.L., Tolstoshev, P., Jaye, M., De la Salle, H. and Lecocq, J.P. (1984). Carrier detection of hemophilia B by using a restriction site polymorphism associated with the coagulation factor IX gene. J. Clin. Invest. 73: 1491-1495.

Kasper, C.K., Osterud, B., Miname, J.Y., Shonick, W.E. and Rapaport, S.I. (1977). Haemophilia B: characterization of carriers. Blood 50: 351-366.

Laurell, C.B. (1972). Electroimmunoassay. Scand. J. Clin. Lab. Invest. 29 (Suppl. 124): 21-37.

Meyer, D. and Larrieu, M.J. (1971). Factor VIII and IX variants. Relationship between Haemophilia BM and Haemophilia B+. Eur. J. Clin. Invest. 1: 425-431.

Peake, I.R., Furlong, B.L. and Bloom, A.L. (1984). Camer detection by direct gene analysis in a family with Haemophilia B (Factor IX deficiency). Lancet 8371(1): 242-243.

Rizza, C.R. and Spooner, R.J.D. (1983). Treatment of haemophilia and related disorders in Britain and northern Ireland during 1976-1980: a report on behalf of the Directors of Haemophilia Centres in the United Kingdom. Br.1Ked J. 286: 929-933.

Simpson, N. and Biggs, R. (1962). The inheritance of christmas factor. Br. J. HaematoL 8: 191203.

Veltkamp, J.L., Drion, E.F. and Loeliger, E. (1968). Detection of the carrier state in hereditary coagulation disorders. Thromb. Diath. Haemorrh. 19: 403-422.

* Part of the Ph.D. Thesis presented by N.F. to the Oxford Haemophilia Centre, Oxford, England