Variant burden and severity of cardiomyopathy in patients with DMD-related Duchenne muscular dystrophy
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Le résumé fourni par la source
BACKGROUND: This study was designed to identify genes for further study as modifiers of the severity of cardiomyopathy in DMD-related Duchenne Muscular Dystrophy (DMD). METHODS: We evaluated genome sequencing results in a well-phenotyped DMD cohort with severe cardiomyopathy against those with less severe cardiomyopathy. Using combined annotation-dependent depletion variant annotation to look at variant burden, we created a difference between group mean (DBGM) summative C-Scores by gene. We completed analyses on three groups. For each analysis, we normalized DBGM summative C-Score and determined which genes had a value > three standard deviations from the mean in all three analyses. RESULTS: There were 54 DMD males in this analysis. 18 individuals (33%) had severe cardiomyopathy and 36 individuals (67%) had less severe cardiomyopathy. Nine genes were identified as possible cardiomyopathy severity modifiers: ANKLE1, ESRRA, FRAS1, GEMIN4, GXYLT1, MTCH2, PKD1L2, PRSS2 and QRFPR. CONCLUSION: DBGM summative C-Scores in well-phenotyped groups are a feasible exploratory method to identify genetic targets for additional study. There is preliminary evidence from this and other studies suggesting further evaluation of ESRRA, GEMIN4, and MTCH2 as modifiers of cardiomyopathy severity could advance understanding of DMD cardiomyopathy progression. IMPACT: This article identifies possible genetic modifiers of DMD cardiomyopathy severity via a novel method of looking at variant burden between groups. This adds to the existing literature by providing new evidence for modifier pathway targets for possible therapeutic targets or drug repurposing in a rare genetic disorder.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Variant burden and severity of cardiomyopathy in patients with DMD-related Duchenne muscular dystrophy
- Date Crossref
- 07/01/2026
- Éditeur
- Springer Science and Business Media LLC
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Riley Hospital for Children Riley Heart Center pays non établi dans la noticeÉtablissement de santé
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Indiana University – Purdue University Indianapolis pays non établi dans la noticeUniversité ou école supérieure
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Indiana University School of Medicine Department of Medical and Molecular Genetics pays non établi dans la noticeUniversité ou école supérieure
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Purdue University West Lafayette pays non établi dans la noticeUniversité ou école supérieure
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Vanderbilt University Medical Center Division of Pediatric Cardiology pays non établi dans la noticeÉtablissement de santé
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Weldon School of Biomedical Engineering pays non établi dans la noticeUniversité ou école supérieure
Riley Heart Center — Riley Hospital for Children, Indiana University – Purdue University Indianapolis et Department of Medical and Molecular Genetics — Indiana University School of Medicine, avec 3 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.