Coexistence of a novel homozygous nonsense mutation in exon 13 of the factor V gene with the homozygous Leiden mutation in two unrelated patients with severe factor V deficiency

A novel homozygous 3571C-->T nonsense mutation predicting the synthesis of a truncated factor V (FV) molecule was identified in exon 13 of the human c oagulation factor V gene in two unrelated Italian probands with undetectabl e plasma levels of FV antigen and activity. Both patients were also homozyg ous for the FV Leiden mutation. Reverse transcription polymerase chain reac tion studies showed strongly reduced mRNA levels of the mutant FV allele an d FV heavy and light chains were not measurable in the plasma of the proban ds and reverse transcriptase. Haplotype analysis-indicated that the nonsens e mutation in both families had a common founder a long time ago.