<abstract xmlns="http://www.w3.org/1999/xhtml"><p>Coagulation factor VII (FVII) is a key enzyme of the extrinsic coagulation cascade that is predominantly produced by hepatocytes. The <italic>F7</italic> gene mutations cause FVII deficiency with considerable molecular and phenotypic heterogeneity. We characterized the molecular alterations of the <italic>F7</italic> 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 <italic>F7</italic> 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 <italic>F7</italic> 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.</p></abstract>

Coagulation factor VII (FVII) is a key enzyme of the extrinsic coagulation cascade that is predominantly produced by hepatocytes. The F7 gene mutations cause FVII deficiency with considerable molecular and phenotypic heterogeneity. We characterized the molecular alterations of the F7 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 F7 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 F7 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.

Molecular characterization of iranian patients with inherited coagulation factor VII deficiency

Balkan Journal of Medical Genetics

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Coagulation factor VII (FVII) is a key enzyme of the extrinsic coagulation cascade that is predominantly produced by hepatocytes. The F7 gene mutations cause...

Molecular characterization of iranian patients with inherited coagulation factor VII deficiency

Article Category: Original Article

Online veröffentlicht: 29. Dez. 2017

Seitenbereich: 19 - 25

DOI: https://doi.org/10.1515/bjmg-2017-0027

Schlüsselwörter
Coagulation factor VII (FVII) deficiency, gene, mRNA sequencing, Mutation detection

© 2017 Shahbazi S, Mahdian R, Karimi K, Mashayekhi A, published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Molecular characterization of iranian patients with inherited coagulation factor VII deficiency

Article Category: Original Article

Online veröffentlicht: 29. Dez. 2017

Seitenbereich: 19 - 25

DOI: https://doi.org/10.1515/bjmg-2017-0027

SchlüsselwörterCoagulation factor VII (FVII) deficiency, gene, mRNA sequencing, Mutation detection

© 2017 Shahbazi S, Mahdian R, Karimi K, Mashayekhi A, published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Schlüsselwörter
Coagulation factor VII (FVII) deficiency, gene, mRNA sequencing, Mutation detection