Molecular characterization of iranian patients with inherited coagulation factor VII deficiency

Coagulation factor VII (FVII) is a key enzyme of the extrinsic coagulation cascade that is predominantly produced by hepatocytes. The gene mutations cause FVII deficiency with considerable molecular and phenotypic heterogeneity. We characterized the molecular alterations of the gene and their corres...

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Bibliographic Details
Published in:Balkan journal of medical genetics 2017-12, Vol.20 (2), p.19-25
Main Authors: Shahbazi, S, Mahdian, R, Karimi, K, Mashayekhi, A
Format: Article
Language:English
Subjects:
Coagulation
Coagulation factor VII
Coagulation factor VII (FVII) deficiency
Coagulation factors
Exons
f7 gene
gene
Gene expression
Hepatocytes
Missense mutation
mRNA sequencing
Mutation
Mutation detection
Original
Polymerase chain reaction
Transcription
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Summary:Coagulation factor VII (FVII) is a key enzyme of the extrinsic coagulation cascade that is predominantly produced by hepatocytes. The gene mutations cause FVII deficiency with considerable molecular and phenotypic heterogeneity. We characterized the molecular alterations of the gene and their corresponding mRNA transcripts in Iranian patients from eight unrelated families. The mutations were detected by polymerase chain reaction (PCR)-sequencing of all gene exons, their flanking intronic sequences, as well as their corresponding cDNA fragments. 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 and patient 8 was a compound heterozygote for R304Q and IVS7+7A>G mutations. 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 also asymptomatic. The mRNA expression analysis revealed that, except the transcript of V(–39)I, other mutation-harboring transcripts were expressed at detectable levels. In conclusion, this report reinforces the genetic and phenotypic heterogeneity of FVII deficiency. The findings of the mRNA study implied that decreased FVII protein activity subsequent to missense mutations does not completely reflect the degradation of mutation-harboring mRNA.
ISSN:1311-0160
2199-5761
1311-0160
DOI:10.1515/bjmg-2017-0027