Clinical Phenotype and Genetic Analysis of Twins With Congenital Coagulation Factor V Deficiency

J Pediatr Hematol Oncol. 2022 Mar 1;44(2):e482-e486. doi: 10.1097/MPH.0000000000002261.

Abstract

Objective: The aim was to investigate the clinical characteristics and molecular pathogenic mechanism of twins with congenital factor V (FV) deficiency.

Methods: We comprehensively analyzed the clinical manifestations and laboratory test results of a set of twins and their parents and performed point mutation analysis with direct high-throughput exon sequencing.

Results: The prothrombin time and activated partial thromboplastin time were prolonged for both probands, and the FV activity levels were 13.0% and 9.8%. Next-generation sequencing showed that the affected individuals harbored a paternal c.5113A>C (p.S1705R) and a maternal c.4949C>T (p.A1650V) heterozygous variants in the FV gene, which conformed to an autosomal recessive inheritance pattern. This is the first report of these point mutations. The older boy also had a congenital patent foramen ovale.

Conclusion: In this set of twins, missense mutations of the FV gene were related to congenital FV deficiency but unrelated to the patent foramen ovale observed in the older boy.

Publication types

  • Twin Study

MeSH terms

  • Activated Protein C Resistance
  • Calmodulin-Binding Proteins / genetics*
  • Factor V / genetics
  • Factor V Deficiency* / congenital
  • Factor V Deficiency* / genetics
  • Foramen Ovale, Patent*
  • Heterozygote
  • Humans
  • Microfilament Proteins / genetics*
  • Mutation
  • Pedigree
  • Phenotype

Substances

  • Calmodulin-Binding Proteins
  • MARCKSL1 protein, human
  • Microfilament Proteins
  • Factor V

Supplementary concepts

  • Thrombophilia due to Activated Protein C Resistance