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.
The complete absence of a coagulation factor probably occurs only with large gene deletions   "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.
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.