Molecular Characterization of Coagulation Factor V and Combined Factors V and VIII Deficiencies in the Northeast of Iran

Background: The deficiencies of Factor V (F5) and combined Factors V and VIII (F5F8D) are known as two rare bleeding disorders. This study aimed to evaluate the studied patients' demographic, laboratory data, and nucleotide changes. Materials and Methods: This is a cross-sectional study of twelve and five patients affected by F5 deficiency and F5F8D, respectively. The study was conducted at Mashhad University of Medical Sciences, from 2015 to 2016. The mean age of the patients with F5 deficiency was 33.91 ± 18.94 years, and that of the patients with F5F8D was 29.40 ± 9.20 years. The coagulation factor assay was performed, and all the exons and intron-exon junctions of LMAN1, MCFD2, and Factor V genes were amplified and subsequently sequenced. Results: The prevalence of F5 deficiency and F5F8D in the Khorasan Razavi population was 7 and 5 per 1,000,000, respectively, which is higher than the estimated worldwide prevalence of 1 per 1,000,000 to 2 per 2,000,000. There were c.2051 G > A, c.6305 G > A, and c.1340 C > G found in the patients with F5 deficiency. Also, those with F5F8D were found to have c.822 G > A and c.149 +1 G > A. Conclusion: The most common nucleotide change in the patients with F5 deficiency was the missense mutation c.6305 G>A in the C2 domain of exon 23 of the factor V gene. In contrast, patients with F5F8D exhibited splice site mutations, specifically c.822 G>A and c.149 +1 G>A, with homozygous inheritance. These findings suggest a distinct genetic pattern for each disorder within the Khorasan Razavi population. To better understand the correlation between factor levels and these nucleotide changes, and to explore the genetic background of other patients, further research involving a larger cohort and more advanced genetic tools, such as whole exome sequencing, is recommended.