Diversity of Dystrophin Gene Mutations and Disease Progression in a Contemporary Cohort of Duchenne Muscular Dystrophy.
Cardiomyopathy
Duchenne Muscular Dystrophy
Dystrophin
Genetics
Journal
Pediatric cardiology
ISSN: 1432-1971
Titre abrégé: Pediatr Cardiol
Pays: United States
ID NLM: 8003849
Informations de publication
Date de publication:
Apr 2022
Apr 2022
Historique:
received:
28
02
2021
accepted:
24
11
2021
pubmed:
23
1
2022
medline:
15
4
2022
entrez:
22
1
2022
Statut:
ppublish
Résumé
Abnormal dystrophin production due to mutations in the dystrophin gene causes Duchenne Muscular Dystrophy (DMD). Cases demonstrate considerable genetic and disease progression variability. It is unclear if specific gene mutations are prognostic of outcomes in this population. We conducted a retrospective cohort study of DMD patients followed at 17 centers across the USA and Canada from 2005 to 2015 with goal of understanding the genetic variability of DMD and its impact on clinical outcomes. Cumulative incidence of clinically relevant outcomes was stratified by genetic mutation type, exon mutation location, and extent of exon deletion. Of 436 males with DMD, 324 (74.3%) underwent genetic testing. Deletions were the most common mutation type (256, 79%), followed by point mutations (45, 13.9%) and duplications (23, 7.1%). There were 131 combinations of mutations with most mutations located along exons 45 to 52. The number of exons deleted varied between 1 and 52 with a median of 3 exons deleted (IQR 1-6). Subjects with mutations starting at exon positions 40-54 had a later onset of arrhythmias occurring at median age 25 years (95% CI 18-∞), p = 0.01. Loss of ambulation occurred later at median age of 13 years (95% CI 12-15) in subjects with mutations that started between exons 55-79, p = 0.01. There was no association between mutation type or location and onset of cardiac dysfunction. We report the genetic variability in DMD and its association with timing of clinical outcomes. Genetic modifiers may explain some phenotypic variability.
Identifiants
pubmed: 35064276
doi: 10.1007/s00246-021-02797-6
pii: 10.1007/s00246-021-02797-6
doi:
Substances chimiques
Dystrophin
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
855-867Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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