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Dystrophin genotype-cardiac phenotype correlations in Duchenne and Becker muscular dystrophy using cardiac magnetic resonance imaging

Tandon, Animesh
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1396453528

Abstract Details

2014, MS, University of Cincinnati, Medicine: Clinical and Translational Research.
Background: Duchenne and Becker muscular dystrophy (DBMD) are caused by mutations in dystrophin. Cardiac manifestations vary broadly across the population, making prognosis difficult. Current dystrophin genotype-cardiac phenotype correlations are limited. For skeletal muscle, the reading-frame rule suggests that in-frame mutations tend to yield milder phenotypes. Methods: A translational model was applied to patient-specific deletion, indel, and nonsense mutations to predict exons and protein domains present within the truncated dystrophin protein. Patients were dichotomized into predicted present and predicted absent groups for exons and protein domains of interest. Development of myocardial fibrosis (represented by late gadolinium enhancement (LGE)) and depressed left ventricular ejection fraction (LVEF) on CMR was compared. Findings: Patients (total n=274) with predicted present cysteine-rich domains (CRD) (n=34), C-terminal domains (CTD) (n=30), and both actin-binding domain 1 and cysteine-rich domain (ABD1+CRD) (n=21) had a decreased risk of LGE and trended toward greater freedom from LGE. Patients with in-frame mutations exactly overlapped with those with CTD predicted present. Patients with predicted present C-terminal domain/in-frame mutations and N-terminal actin-binding+cysteine-rich domains trended towards decreased risk of and greater freedom from depressed LVEF. Interpretation: Genotypes previously implicated in altering DBMD cardiac phenotype were not significantly related to LGE and depressed LVEF. Patients with predicted present cysteine-rich domain, C-terminal domain/in-frame mutations, and N-terminal actin-binding+cysteine-rich domains trended toward greater freedom from LGE and depressed LVEF, suggesting that the DBMD reading-frame rule may be applicable to the cardiac phenotype. Genotype-phenotype correlations may help predict the cardiac phenotype for DBMD patients and guide future therapies.
Erin Nicole Haynes, Dr. P.H. (Committee Chair)
Zhiqian Gao, Ph.D. MSPH (Committee Member)
Michael Taylor, M.D. Ph.D. (Committee Member)
28 p.
Surgery
Duchenne muscular dystrophy; left ventricular ejection fraction; cardiac magnetic resonance imaging

Recommended Citations

Citations

  • Tandon, A. (2014). Dystrophin genotype-cardiac phenotype correlations in Duchenne and Becker muscular dystrophy using cardiac magnetic resonance imaging [Master's thesis, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1396453528

    APA Style (7th edition)

  • Tandon, Animesh. Dystrophin genotype-cardiac phenotype correlations in Duchenne and Becker muscular dystrophy using cardiac magnetic resonance imaging. 2014. University of Cincinnati, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1396453528.

    MLA Style (8th edition)

  • Tandon, Animesh. "Dystrophin genotype-cardiac phenotype correlations in Duchenne and Becker muscular dystrophy using cardiac magnetic resonance imaging." Master's thesis, University of Cincinnati, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1396453528

    Chicago Manual of Style (17th edition)

ucin1396453528
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© 2014, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.