The ACTN3 577XX Null Genotype Is Associated with Low Left Ventricular Dilation-Free Survival Rate in Patients with Duchenne Muscular Dystrophy
Section snippets
Methods
This was a single-center retrospective study. Patients with DMD were registered at the Department of Pediatrics, Kobe University Hospital, between June 1992 and March 2018. The medical records of registered patients with DMD were reviewed retrospectively. The clinical diagnosis of DMD was confirmed by the identification of mutations in DMD. Gene mutations were analyzed in both genomic DNA and mRNA extracted from the muscle or peripheral lymphocytes, as previously described.22 The reading frame
Results
The patients who were diagnosed with DMD and registered in our hospital numbered 452. Genomic DNA from 163 patients with DMD was available for ACTN3 variant analysis. Of 163 patients, 74 patients were excluded because they underwent routine echocardiographic examinations at local hospitals. In addition, 12 patients had evidence of cardiac dysfunction at the time of first echocardiography, and they were excluded because the onset age of cardiac involvement was unknown. A total of 77 patients
Discussion
This study found an association between the ACTN3 577XX null genotype and early progression of DCM in DMD. In the present study, the ACTN3 genotype was determined in the 77 patients with DMD, and the cardiac involvement-free survival rate was compared among genotypes. We observed a significantly earlier progression to LV dilation in patients with the ACTN3 null genotype.
We determined the ACTN3 genotype of 163 enrolled patients, and the allele frequency of R577X was 0.552. The R577X allele
Funding Sources
This study was supported by the Japanese Society for the Promotion of Science Grants-in-Aid for Scientific Research (KAHEN-HI, #18K07845 and #19K17564) and an Intramural Research Grant for Neurological and Psychiatric Disorders from the National Center of Neurology and Psychiatry (#29-3).
Disclosures
Dr. Matsuo is an advisor for JCR Pharma, Japan, and Daiichi Sankyo, Japan. The other authors report no conflicts of interest.
Acknowledgments
We are thankful to the families who participated in this study.
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Cardiorespiratory management of Duchenne muscular dystrophy: emerging therapies, neuromuscular genetics, and new clinical challenges
2022, The Lancet Respiratory MedicineCitation Excerpt :However, by promoting a shift in muscles towards slow-fibre characteristics, including better recovery from fatigue, α-actinin-3 deficiency might confer improved muscle endurance and have a protective effect on the progressive muscle damage that characterises DMD.104,132 In a study of 77 patients with DMD, earlier onset of cardiomyopathy and left ventricular dilatation was associated with α-actinin-3 deficiency due to homozygosity of Arg577Ter.119 This finding suggests that ACTN3 might be a beneficial modifier of long-term DMD skeletal muscle function, but a detrimental modifier of DMD cardiac function.
Is it time for genetic modifiers to predict prognosis in Duchenne muscular dystrophy?
2023, Nature Reviews NeurologyDMD Gene and Dystrophinopathy Phenotypes Associated With Mutations: A Systematic Review for Clinicians
2023, Journal of Clinical Neuromuscular Disease
FANTOM5, https://fantom.gsc.riken.jp/5/, Library ID; CNhs11790, accecced at Feb/20/2020
GEO profiles, https://www.ncbi.nlm.nih.gov/geoprofiles, ID27912914, accecced at Feb/20/2020