GENETIC DIAGNOSTICS OF HEMOPHILIA A
Abstract
Background. Hemophilia A is a chromosome X-linked bleeding disorder due to mutations in the FVIII gene. There are 163 hemophilia A patients in Slovene registry for Hemophilia. 74 have severe hemophilia A and 50% of patients with severe hemophilia A have inversion of intron 22 that is detected using the LD-PCR method. Point mutations are detected by amplification of exons of the factor VIII gene followed with a direct sequencing technique.
Results. In the Slovene population we managed to determine a genetic mutation in 67/163 patients, 36/67 have inversion of intron 22 and another 31/67 have 12 different point mutations in the FVIII gene which cause hemophilia A. Three of them are so far found only among Slovene patients.
Conclusions. The identification of hemophilia mutations is of great importance for the timely discovery of the hemophilia carriers and the pre-natal diagnostics of hemophilia A.
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References
Stamatoyannopoulos G, Niehuis AW, Majerus PW, Varmus H. The molecular basis of blood diseases. 2nd ed. Philadelphia: W.B: Saunders Company, The Curtis Centre, Independance Squere West, 1994: 890–8.
Gitscher J, Wood WI, Goralka TM et al. Characterisation of the human factor VIII gene. Nature 1984; 312: 326–30.
Lakich D, Kazazian HH, Antonarakis SE, Gitschier J. Inversions disrupting the factor VIII gene are common cause of severe Haemophilia A. Nature Genetics 1993; 5: 236–41.
Antonarakis SE, Rossiter JP, Young M et al. Factor VIII inversions in severe hemophilia A: results from an international consortium. Blood 1995; 86: 2206–12.
HAMSTeRS (angl. Haemophilia A Mutation Search, Test and Resource Site), http://europium.rpms.ac.uk
Miller SA, Dyches DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucl Acids Res 1988; 16: 1215–5.
Davies KE. Human genetic diseases. A practical approach. Oxford: IRL Press Limited, 1987: 245–5.
Liu Q, Sommer SS. Subcycling-PCR for multiplex long distance amplification of regions with high and low GC content application to the inversion hotspot in the FVIII gene. Biotechniques 1998; 25: 1022–8.
Strmecki L. Iskanje in opredelitev mutacij gena za koagulacijski faktor VIII pri hemofiliji A. Doktorsko delo. Ljubljana: Medicinska fakulteta, 1998: 95–106.
Rossiter JP, Young M, Kimberland ML et al. Factor VIII gene inversions causing severe hemophilia A originate almost exclusively in male germ cells. Hum Molec Genet 1994; 3: 1035–9.
Strmecki L, Benedik-Dolničar M, Vidan-Jeras B, Komel R. Inversions of the factor VIII gene in Slovenian patients with severe haemophilia A. Eur J Haematol 1999; 63: 64–6.
Youssoufian H, Kazazian HH, Phillips DG et al. Recurrent mutations in haemophilia A give evidence for CpG mutation hotspots. Nature 1986; 324: 380–2.
Strmecki L, Benedik-Dolničar M, Komel R. A novel mutation Q602STOP in exon 12 of the FVIII gene. Human Heredity 1998; 48: 119–20.
Strmecki L, Benedik-Dolničar M, Vouk K, Komel R. Screen of 55 Slovenian haemophilia A patients: identification of 2 novel mutations (S-1R and IVS23+1G›A) and discussion of mutation spectrum. Hum Mutat 1999; 13: 413–3.
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