| |
| |
| genotype-phenotype
correlation |
| Genotype-phenotype
relationships for RBDs are not well established. Patients with
RBDs and clinically significant manifestations are usually homozygous
or compound heterozygous. |
|
Heterozygotes (parents and children of the probands) have approximately
half-normal levels of coagulation factors and are usually asymptomatic,
although a recent North American survey found a relatively high
rate of bleeding symptoms 7.
|
| The
complete absence of a coagulation factor probably occurs only
with large gene deletions 8.
|
| "Null"
mutations predicting the production of truncated proteins or
of unstable mRNAs (partial deletions, out-of-frame insertions,
splicing abnormalities, nonsense mutations) are usually associated
with very low or undetectable plasma factor and severe clinical
manifestations 2
. |
| The effect of missense mutations is less homogenous: while in some instances they lead to severe factor deficiency, in others they are associated with partial deficiencies and milder clinical manifestations. |
|
