Balkan Journal of Medical Genetics

MOLECULAR CHARACTERIZATION OF IRANIAN PATIENTS WITH INHERITED COAGULATION FACTOR VII DEFICIENCY
Shahbazi S1,*, Mahdian R2, Karimi K3, Mashayekhi A1
*Corresponding Author: Dr. Shirin Shahbazi, Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Al-e-Ahmad and Chamran Cross, POB 14115-111Tehran, Iran. Tel: +98-21-82-884-556. Fax: +98-21- 82-884-555. E-mail: sh.shahbazi@modares.ac.ir
page: 19

RESULTS

Patients. Table 3 shows clinical information and FVII activity levels of each patient. As shown, the severity of symptoms was not directly correlated with FVII activity levels. Chronic nosebleeds, easy bruising and bleeding from the gums were the most common symptoms. Patient 4 was the only asymptomatic patient in our study. He was diagnosed following pre surgery blood analysis. Patient 3 was a female patient who developed menorrhagia as the main clinical manifestation. Patient 2 and patient 6 were born from consanguineous marriages. F7 Mutation Status Detected by Polymerase Chain Reaction-Sequencing. Eight different F7 gene mutations were detected in our study patients. The mutations and their corresponding amino acid changes are summarized in Table 4. Homozygous P303T, C91S and R304Q mutations were detected in patient 2, patient 5 and patient 6, respectively. Patient 7 was a compound heterozygote for S282R and H348R. Another compound heterozygous mutation was detected in patient 8 with R304Q and IVS7+7A>G alterations. Furthermore, our investigation revealed three heterozygous individuals, patient 1 and patient 3 with the A244V mutation who were symptomatic and patient 4 with V(–39)I mutation who was asymptomatic. The F7 cDNA Analysis. Despite the low level of F7 transcript in peripheral blood cells, the extraction and amplification of F7 mRNA were successfully performed. We expected the amplification of alternative isoforms of F7 mRNA according to the presence or absence of exon 1b. Although the only observed mRNA isoform was the transcript lacking exon 1b. Direct sequencing of PBMC-derived cDNA for A244V, S282K, H348Q and R304Q mutations revealed equal expression of wild-type and mutant allele transcripts. These variants were detected in the compound heterozygous and heterozygous patients. In addition, the cDNA analysis in homozygous patients indicated that mutationharboring transcripts, i.e., P303T, C91S and R304Q, were also detectable. In contrast, cDNA sequencing of the 64G>A heterozygote mutation showed the absence of the mutated allele transcript in patient 4. The sequencing chromatogram shown in Figure 1 presents 64G>A in the genomic DNA and its absence in the corresponding cDNA. Evaluation of transcript following the IVS7+7A>G variant that was detected in patient 8 showed a cDNA with normal pattern.

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