2% Hämophilie-A-Patienten ohne Mutation im FVIII-Gen

TY - JOUR

T1 - 2% Hämophilie-A-Patienten ohne Mutation im FVIII-Gen

AU - Uen, C

AU - Oldenburg, J

AU - Schröder, J

AU - Brackmann, H-J

AU - Schramm, W

AU - Schwaab, R

AU - Schneppenheim, R

AU - Graw, J

PY - 2003/2/1

Y1 - 2003/2/1

N2 - In Germany, approximately 6,000 patients are suffering from haemophilia A. Screening methods cover 97% of the mutations. For the other patients the coding sequences of the FVIII gene have to be sequenced in total. Out of 1,350 patients, no mutation was observed in 80 patients. In 5 patients, we observed an inversion in intron 1. Known mutations were detected in 16 patients, and in 19 cases novel mutations were characterized (14 in coding regions and 5 in flanking introns). The mutations are mainly base pair substitutions, small deletions or insertions (max. 4 bp) and predicted to cause amino acid exchanges or frameshifts leading to premature stop codons. Moreover, 5 polymorphisms were identified in exons 14 and 26 as well as in introns 7 and 19. Further studies are necessary to identify their causative effects. Surprisingly, in 23 patients out of this subgroup of 80, no mutation was identified in the FVIII gene. Therefore, mutations in non-coding areas or even in other genes have to be considered responsible for the haemophilia A like phenotype. One of them codes for the von Willebrand factor (vWF). We confirmed in two of our cases mutations in the vWF gene.

AB - In Germany, approximately 6,000 patients are suffering from haemophilia A. Screening methods cover 97% of the mutations. For the other patients the coding sequences of the FVIII gene have to be sequenced in total. Out of 1,350 patients, no mutation was observed in 80 patients. In 5 patients, we observed an inversion in intron 1. Known mutations were detected in 16 patients, and in 19 cases novel mutations were characterized (14 in coding regions and 5 in flanking introns). The mutations are mainly base pair substitutions, small deletions or insertions (max. 4 bp) and predicted to cause amino acid exchanges or frameshifts leading to premature stop codons. Moreover, 5 polymorphisms were identified in exons 14 and 26 as well as in introns 7 and 19. Further studies are necessary to identify their causative effects. Surprisingly, in 23 patients out of this subgroup of 80, no mutation was identified in the FVIII gene. Therefore, mutations in non-coding areas or even in other genes have to be considered responsible for the haemophilia A like phenotype. One of them codes for the von Willebrand factor (vWF). We confirmed in two of our cases mutations in the vWF gene.

KW - Base Sequence

KW - Codon

KW - DNA

KW - DNA Transposable Elements

KW - Factor VIII

KW - Genetic Testing

KW - Germany

KW - Hemophilia A

KW - Humans

KW - Incidence

KW - Introns

KW - Mutation

KW - Polymerase Chain Reaction

KW - Polymorphism, Genetic

KW - Sequence Deletion

U2 - 10.1267/Hamo03010001

DO - 10.1267/Hamo03010001

M3 - SCORING: Zeitschriftenaufsatz

C2 - 12567191

VL - 23

SP - 1

EP - 5

JO - HAMOSTASEOLOGIE

JF - HAMOSTASEOLOGIE

SN - 0720-9355

IS - 1

ER -