PMID- 25702278
OWN - NLM
STAT- MEDLINE
DCOM- 20150519
LR  - 20220408
IS  - 1879-1913 (Electronic)
IS  - 0002-9149 (Print)
IS  - 0002-9149 (Linking)
VI  - 115
IP  - 7
DP  - 2015 Apr 1
TI  - Dystrophin genotype-cardiac phenotype correlations in Duchenne and Becker 
      muscular dystrophies using cardiac magnetic resonance imaging.
PG  - 967-71
LID - S0002-9149(15)00065-X [pii]
LID - 10.1016/j.amjcard.2015.01.030 [doi]
AB  - Duchenne and Becker muscular dystrophies are caused by mutations in dystrophin. 
      Cardiac manifestations vary broadly, making prognosis difficult. Current 
      dystrophin genotype-cardiac phenotype correlations are limited. For skeletal 
      muscle, the reading-frame rule suggests in-frame mutations tend to yield milder 
      phenotypes. We performed dystrophin genotype-cardiac phenotype correlations using 
      a protein-effect model and cardiac magnetic resonance imaging. A translational 
      model was applied to patient-specific deletion, indel, and nonsense mutations to 
      predict exons and protein domains present within 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) were compared. Patients (n = 274) with predicted present 
      cysteine-rich domain (CRD), C-terminal domain (CTD), and both the N-terminal 
      actin-binding and cysteine-rich domains (ABD1 + CRD) had a decreased risk of LGE 
      and trended toward greater freedom from LGE. Patients with predicted present CTD 
      (exactly the same as those with in-frame mutations) and ABD1 + CRD trended toward 
      decreased risk of and greater freedom from depressed LVEF. In conclusion, 
      genotypes previously implicated in altering the dystrophinopathic cardiac 
      phenotype were not significantly related to LGE and depressed LVEF. Patients with 
      predicted present CRD, CTD/in-frame mutations, and ABD1 + CRD trended toward 
      milder cardiac phenotypes, suggesting that the reading-frame rule may be 
      applicable to the cardiac phenotype. Genotype-phenotype correlations may help 
      predict the cardiac phenotype for dystrophinopathic patients and guide future 
      therapies.
CI  - Copyright (c) 2015 Elsevier Inc. All rights reserved.
FAU - Tandon, Animesh
AU  - Tandon A
AD  - The Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, 
      Ohio.
FAU - Jefferies, John L
AU  - Jefferies JL
AD  - The Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, 
      Ohio.
FAU - Villa, Chet R
AU  - Villa CR
AD  - The Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, 
      Ohio.
FAU - Hor, Kan N
AU  - Hor KN
AD  - The Heart Center, Nationwide Children's Hospital, Columbus, Ohio.
FAU - Wong, Brenda L
AU  - Wong BL
AD  - Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, 
      Ohio.
FAU - Ware, Stephanie M
AU  - Ware SM
AD  - The Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, 
      Ohio; Division of Human Genetics, Cincinnati Children's Hospital Medical Center, 
      Cincinnati, Ohio.
FAU - Gao, Zhiqian
AU  - Gao Z
AD  - The Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, 
      Ohio.
FAU - Towbin, Jeffrey A
AU  - Towbin JA
AD  - The Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, 
      Ohio.
FAU - Mazur, Wojciech
AU  - Mazur W
AD  - The Heart and Vascular Center at the Christ Hospital, Cincinnati, Ohio.
FAU - Fleck, Robert J
AU  - Fleck RJ
AD  - Department of Radiology, Cincinnati Children's Hospital Medical Center, 
      Cincinnati, Ohio.
FAU - Sticka, Joshua J
AU  - Sticka JJ
AD  - The Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, 
      Ohio.
FAU - Benson, D Woodrow
AU  - Benson DW
AD  - Herma Heart Center, Children's Hospital of Wisconsin, Milwaukee, Wisconsin.
FAU - Taylor, Michael D
AU  - Taylor MD
AD  - The Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, 
      Ohio. Electronic address: Michael.Taylor1@cchmc.org.
LA  - eng
GR  - UL1 RR026314/RR/NCRR NIH HHS/United States
GR  - UL1 TR000077/TR/NCATS NIH HHS/United States
GR  - UL1 TR001425/TR/NCATS NIH HHS/United States
PT  - Journal Article
DEP - 20150115
PL  - United States
TA  - Am J Cardiol
JT  - The American journal of cardiology
JID - 0207277
RN  - 0 (Dystrophin)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Cardiomyopathies/*diagnosis/etiology/genetics
MH  - Child
MH  - Child, Preschool
MH  - DNA/*genetics
MH  - DNA Mutational Analysis
MH  - Dystrophin/*genetics/metabolism
MH  - Exons
MH  - Female
MH  - Humans
MH  - Magnetic Resonance Imaging
MH  - Magnetic Resonance Imaging, Cine/*methods
MH  - Male
MH  - Muscle, Skeletal/*metabolism
MH  - Muscular Dystrophy, Duchenne/complications/*genetics/metabolism
MH  - *Mutation
MH  - Sequence Deletion
MH  - Young Adult
PMC - PMC5568575
MID - NIHMS896074
COIS- Disclosures The authors have no conflicts of interest to disclose.
EDAT- 2015/02/24 06:00
MHDA- 2015/05/20 06:00
PMCR- 2017/08/23
CRDT- 2015/02/23 06:00
PHST- 2014/10/20 00:00 [received]
PHST- 2015/01/06 00:00 [revised]
PHST- 2015/01/06 00:00 [accepted]
PHST- 2015/02/23 06:00 [entrez]
PHST- 2015/02/24 06:00 [pubmed]
PHST- 2015/05/20 06:00 [medline]
PHST- 2017/08/23 00:00 [pmc-release]
AID - S0002-9149(15)00065-X [pii]
AID - 10.1016/j.amjcard.2015.01.030 [doi]
PST - ppublish
SO  - Am J Cardiol. 2015 Apr 1;115(7):967-71. doi: 10.1016/j.amjcard.2015.01.030. Epub 
      2015 Jan 15.