correlation

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.