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Genotyping of Intron Inversions and Point Mutations in Exon 14 of the FVIII Gene in Iranian Azeri Turkish Families with Hemophilia A

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Abstract

Hemophilia A (HA) is an inherited X-linked bleeding disorder caused by a variety of mutations that are distributed throughout the large FVIII gene (F8). The most common mutations in studied populations with severe HA are introns 22 and 1 inversions, gross exon deletions and point mutations in exon 14. The aim of this study was to define the frequency of these common mutations in Iranian population of Azeri Turkish in North West of Iran. Fifty patients with severe HA and forty-three female potential carriers were genotyped by inverse shifting polymerase chain reaction (IS-PCR), long-range PCR, multiplex PCR, and sequencing methods for the detection of Intron 22 and 1 inversions, gross exon deletions, and exon 14 point mutations, respectively. F8 intron 22 inversion was detected in 22 (44 %) out of 50 patients. Moreover, we detected one intron 1 inversion (2 %), and one point mutation in exon 14 (2 %). In this population, 52 % of the patients with hemophilia A did not show to carry a mutation in the analyzed regions by three mentioned methods. F8 intron 22 inversion was the major causative mutation in nearly 50 % of severe HA cases in an Azerbaijani Turkish population, which is similar to the incidence of other populations. IS-PCR is a robust, rapid, efficient, and cost-effective method for the genetic analysis of patients with severe HA and for HA carrier detection, especially in developing countries.

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Acknowledgments

We extend our sincere thanks to all participating families with HA for their contributions to this study. This study was supported by grants from the Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

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Authors and Affiliations

  1. Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Mahmoud Shekari Khaniani, Abdollah Ebrahimi & Sima Mansoori Derakhshan

  2. Department of Medical Genetics, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

    Mahmoud Shekari Khaniani, Abdollah Ebrahimi & Sima Mansoori Derakhshan

  3. Ebnsina Medical Genetic Center, Outpatient Clinic of Tabriz University of Medical Sciences, Tabriz, Iran

    Setareh Daraei

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  1. Mahmoud Shekari Khaniani
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  2. Abdollah Ebrahimi
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  3. Setareh Daraei
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  4. Sima Mansoori Derakhshan
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Correspondence to Sima Mansoori Derakhshan.

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Shekari Khaniani, M., Ebrahimi, A., Daraei, S. et al. Genotyping of Intron Inversions and Point Mutations in Exon 14 of the FVIII Gene in Iranian Azeri Turkish Families with Hemophilia A. Indian J Hematol Blood Transfus 32, 475–480 (2016). https://doi.org/10.1007/s12288-016-0699-2

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  • DOI: https://doi.org/10.1007/s12288-016-0699-2

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