| |
| |
| genotype |
| Even
though much progress was recently done to unravel the molecular
lesions underlying RBDs (Figure 3)
2
3,
|
| RBDs
are usually due to mutations in the genes that encode the corresponding
coagulation factors. |
| Exceptions
are the combined deficiency of FV and FVIII, characterized by
defects in genes encoding proteins involved in the intracellular
transport of these factors 4
5 and the combined deficiency of vitamin
K-dependent FII, FVII, FIX, and FX, characterized by defects
in the genes encoding enzymes involved in posttranslational
modifications of these factors and in vitamin K metabolism 6
|
| In
contrast to haemophilia A, where inversion events involving
intron 22 or intron 1 of the FVIII gene are responsible for
approximately half of the all cases; RBDs are generally caused
by mutations unique to each kindred 2. |
| In
approximately 10% to 20% of patients, no putative mutation is
found. |
| These
cases may be due to defects in non-coding regions or in genes
coding for regulators of intracellular transport and posttranslational
modifications of coagulation factors. |
| To
date knowledge of the underlying mutation(s) in the affected
gene has not been widely exploited to allow reproductive choices
to be made within kindred by genetic counselling and prenatal
diagnosis |
|
