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Article Number - E48B7E944718


Vol.6(1), pp. 1-10 , May 2014
DOI: 10.5897/CRO11.015
ISSN: 2141-2553



Review

Factor VIII genetic mutations and protein alterations in hemophilia A: A review



Nuzhat Jahan Faridi*
  • Nuzhat Jahan Faridi*
  • Department of Pathology, Ram Manohar Lohia Institute of Medical Sciences Lucknow, India.
  • Google Scholar
Praveen Kumar
  • Praveen Kumar
  • Department of Pathology, Ram Manohar Lohia Institute of Medical Sciences Lucknow, India.
  • Google Scholar
Nuzhat Husain
  • Nuzhat Husain
  • Department of Pathology, Ram Manohar Lohia Institute of Medical Sciences Lucknow, India.
  • Google Scholar
Mohammad Imran Siddiqi
  • Mohammad Imran Siddiqi
  • Department of Pathology, Ram Manohar Lohia Institute of Medical Sciences Lucknow, India.
  • Google Scholar







 Received: 20 April 2011  Accepted: 20 May 2014  Published: 31 May 2014

Copyright © 2014 Author(s) retain the copyright of this article.
This article is published under the terms of the Creative Commons Attribution License 4.0


Hemophilia A represents a severe most common inherited hemorrhagic disorder caused by heterogeneous mutations, which lead to dysfunctional factor VIII protein. Besides the inversion 22 and intron 1 inversion, the mutations may describe 627 missense and 142 nonsense unique mutations. Changes in the protein sequence induce structural or functional impairment. This study aimed to review mutation in different domains and discuss molecular modeling approach to assess the effects of amino acid substitutions on the topology of FVIII protein domains. A comprehensive literature search was done to analyze the mutations and structural alterations reported in the Hemophilia A gene. Further, our experience in small mutation analyzed with structural alterations was added to the review. Mutation types were used at the hemophilia A mutation, structure, test and resource site (HAMSTeRS). Half of the point mutation in the FVIII gene was found in domain A which includes Glu321Lys, Tyr346Cys, Val357Gly, Thr770Ser, Thr751Ser etc. Exon 14 represents about one half of the coding region and encodes for the FVIII B domain. Several recurrent mutations have been found at 2147, 2150, 2159, 2163 {C1} and 2209, 2300, 2307 (C2) amino-acid positions. Different domains play an important role in the function of FVIII as each contains specific binding active site during the clotting cascade. The review brings forth the functional alterations occurring because of causative mutations in hemophilia A gene.

Key words: Hemophilia a, FVIII gene, mutations, protein modeling.

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APA Faridi, N. J., Kumar, P., Husain, N. & Imran, M. (2014). Factor VIII genetic mutations and protein alterations in hemophilia A: A review. Clinical Reviews and Opinions, 6(1), 1-10.
Chicago Nuzhat Jahan Faridi, Praveen Kumar, Nuzhat Husain and Mohammad Imran. "Factor VIII genetic mutations and protein alterations in hemophilia A: A review." Clinical Reviews and Opinions 6, no. 1 (2014): 1-10.
MLA Nuzhat Jahan Faridi, et al. "Factor VIII genetic mutations and protein alterations in hemophilia A: A review." Clinical Reviews and Opinions 6.1 (2014): 1-10.
   
DOI 10.5897/CRO11.015
URL http://academicjournals.org/journal/CRO/article-abstract/E48B7E944718

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