Table 1. Effects of different single... | American Society of Hematology

Table 1.

Effects of different single allele mutations on the mature VWF subunit.

Type of mutation*	Effect on VWF subunit	Consequence at the molecular level
*Mutations occurring at the propeptide level may act through all of the above-mentioned mechanism, but intrinsic molecular abnormality is not expected.
†Sequence variations in regulatory regions of the gene may affect the efficiency of transcription.
Gene deletion or null allele Missense†	No production or unstable protein degraded intracellularly The mutant subunit is not able to dimerize and to be incorporated into the multimer The mutant subunit is variably incorporated into the multimer	Decrease of VWF production a) Decrease of VWF production b1) No or minimal multimeric abnormality b2) Decrease of VWF production due to defective intracellular processing b3) Intrinsic functional abnormality b4) Major effect on multimeric structure due to: - steric hindrance - increased or decreased post-secretion proteolysis

Type of mutation*	Effect on VWF subunit	Consequence at the molecular level
*Mutations occurring at the propeptide level may act through all of the above-mentioned mechanism, but intrinsic molecular abnormality is not expected.
†Sequence variations in regulatory regions of the gene may affect the efficiency of transcription.
Gene deletion or null allele Missense†	No production or unstable protein degraded intracellularly The mutant subunit is not able to dimerize and to be incorporated into the multimer The mutant subunit is variably incorporated into the multimer	Decrease of VWF production a) Decrease of VWF production b1) No or minimal multimeric abnormality b2) Decrease of VWF production due to defective intracellular processing b3) Intrinsic functional abnormality b4) Major effect on multimeric structure due to: - steric hindrance - increased or decreased post-secretion proteolysis