We have located links that may give you full text access.
JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
Sequence and structural properties of identical mutations with varying phenotypes in human coagulation factor IX.
Proteins 2008 October
Mutations in human coagulation factor IX cause an X-linked bleeding disorder Hemophilia B, which can be classified as severe, moderately severe and mild based on the plasma levels of factor IX among affected individuals with respect to normal factor IX activity assayed in the patients' plasma (<1%, 2-5%, 6-30%, respectively). Recently, we identified hemophilia B to be a disease with mutations showing clinical variation and speculated that this phenotypic heterogeneity might be a replacement-specific property. Here, we have analyzed the differences in sequence and structural properties among identical mutations with varying phenotypes (IMVPs) by comparing with mutations with uniform phenotypes (MUPs), with recurring reports in Haemophilia B mutation database. Classification of mutations into IMVPs and MUPs has been done based on rigorous systematic evaluation of the clotting activity each mutation is associated with. IMVPs (n = 51) occur in less conserved mutant sites with more tolerated substitutions compared to MUPs (n = 100). A preponderance of CpG site mutations and Arg as the mutated residue in IMVPs compared to Cys in MUPs was observed. Hence, a CpG site substitution at less conserved Arg site might have an increased propensity of expressing variable phenotypes. The changes in intrinsic properties associated with the mutation are less drastic for IMVPs than for MUPs, though no significant differences were observed in structural properties. Based on this study and available literature we speculate that modifier genes at other loci, epigenetic interactions and environment may serve individually or cumulatively to bring about the clinical variation implicating hemophilia B to be deviation from classical Mendelian disorder with complete penetrance. We demonstrate that phenotypic heterogeneity appears to be site-specific also owing to the lesser conservation of the mutant site.
Full text links
Related Resources
Trending Papers
Heart failure with preserved ejection fraction: diagnosis, risk assessment, and treatment.Clinical Research in Cardiology : Official Journal of the German Cardiac Society 2024 April 12
Proximal versus distal diuretics in congestive heart failure.Nephrology, Dialysis, Transplantation 2024 Februrary 30
World Health Organization and International Consensus Classification of eosinophilic disorders: 2024 update on diagnosis, risk stratification, and management.American Journal of Hematology 2024 March 30
Efficacy and safety of pharmacotherapy in chronic insomnia: A review of clinical guidelines and case reports.Mental Health Clinician 2023 October
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app