Genotype and phenotype report on patients with combined deficiency of factor V and factor VIII in Iran

Combined factor V (FV) and factor VIII (FVIII) deficiency is a rare autosomal recessive bleeding disorder characterized by mild-to-moderate bleeding. Epistaxis, postsurgical bleeding and menorrhagia are the most common symptoms. The aim of this study is to report the phenotype-genotype characterization carried out in patients affected with combined FV and FVIII deficiency from Iran. A cross-sectional study was conducted in Shiraz Hemophilia Center, southern Iran. Twelve cases, seven men and five women coming from eight families were included in our study after taking consent form. Coagulation activity for all patients was measured. All exons and intron-exon junctions of lectin mannose binding protein 1 (LMAN1) gene and multiple coagulation factor deficiency 2 genes were amplified by PCR, and subsequently sequenced by the Sanger method. Patients age ranged from 6 to 59 years mean +/- SD: 23.8 +/- 15.4 years and median: 22 years. No patient presented with severe bleeding symptom. Only one patient had severe FV and FVIII deficiency (both factor levels <1%). Four different type of mutations (duplication, insertion, splice site and nonsense), occurring in different locuses, were identified on LMAN1 gene in 12 Iranian patients. There was a significant correlation between FV and FVIII levels, which is indicative of association with loss of function of LMAN1 gene, and reduced plasma levels of both factors. Our study showed that all of our characterized patients with combined FV and FVIII deficiency present different homozygous mutations on LMAN1 gene introducing a premature stop codon. Larger studies are needed to calculate the correlation between factor levels, genetic and bleeding symptoms.