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Association of genetic mutations and loss of ambulation in childhood-onset dystrophinopathy
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2 2021
Source: Muscle Nerve. 63(2):181-191 -
Alternative Title:Muscle Nerve
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Personal Author:
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Description:Introduction
Quantifying associations between genetic mutations and loss of ambulation (LoA) among males diagnosed with childhood-onset dystrophinopathy is important for understanding variation in disease progression and may be useful in clinical trial design.
Methods
Genetic and clinical data from the Muscular Dystrophy Surveillance, Tracking, and Research Network for 358 males born and diagnosed from 1982–2011 were analyzed. LoA was defined as the age at which independent ambulation ceased. Genetic mutations were defined by overall type (deletion/duplication/point mutation) and among deletions, those amenable to exon-skipping therapy (exons 8, 20, 44–46, 51–53) and another group. Cox proportional hazards regression modeling was used to estimate hazards ratios (HR) and 95% confidence intervals (CI).
Results
Mutation type did not predict time to LoA. Controlling for corticosteroids, Exons 8 (HR=0.22; 95% CI=0.08,0.63) and 44 (HR=0.30; 95% CI=0.12,0.78) were associated with delayed LOA compared to other exon deletions.
Discussion
Delayed LoA in males with mutations amenable to exon-skipping therapy is consistent with previous studies. These findings suggest that clinical trials including exon 8 and 44 skippable males should consider mutation information prior to randomization.
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Pubmed ID:33150975
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Pubmed Central ID:PMC8094042
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