Severe coagulation factor V deficiency caused by 2 novel frameshift mutations: 2952delT in exon 13 and 5493insG in exon 16 of factor 5 gene

A high-throughput sequencing test for diagnosing inherited bleeding, thrombotic, and platelet disorders

“…We considered such variants to be of unproven pathogenicity in a Mendelian disease setting in accordance with current standards. The genes F5, 31,32 ExAC and therefore it cannot underlie a high-penetrance autosomal dominant disorder. Indeed, the authors 41 reporting this mutation observed it in a single pedigree in which 2 cases and no unaffected relatives were screened, and decided that its absence in a mere 45 control samples was sufficient to infer causality for the child's Alport syndrome and the mother's hearing loss.…”

Residual platelet factor V ensures thrombin generation in patients with severe congenital factor V deficiency and mild bleeding symptoms

“…Despite this important observation, platelet FV is not routinely evaluated in FV-deficient patients and only 3 other studies report platelet FV levels in patients with severe FV deficiency. [32][33][34] No platelet FV antigen or activity could be demonstrated in 2 patients with undetectable plasma FV. 32,33 In another FV-deficient patient, platelet FV could be visualized by Western blotting, but its activity was not determined.…”

Arg2074Cys missense mutation in the C2 domain of factor V causing moderately severe factor V deficiency: molecular characterization by expression of the recombinant protein

“…[8][9][10][11][12][13] A possible explanation for the recurrence of the Arg2074Cys mutation is the involvement of a CpG mutation hot spot. On the other hand, the presence of a different mutation not involving a CpG dinucleotide at the same residue in FV (Arg2074His), as well as of several hemophilia A-causing mutations in the corresponding residue of FVIII, points to the important role of this amino acid for FV synthesis and secretion.…”

“…5 The genetic basis of severe or moderately severe type I FV deficiency is still poorly explored (up to now, a total of 12 mutations scattered through F5 have been identified). [8][9][10][11][12][13] Most mutations are nonsense, frameshift, or splicing mutations, giving rise to null alleles, whereas only 3 missense mutations have been identified. An additional 8 mutations causing FV deficiency have been reported in the heterozygous state, 5 of which were found in patients who carried the FV Leiden mutation on the second allele, leading to the "pseudohomozygous APC-resistance" condition.…”