The impact of genotype on age at loss of ambulation in individuals with Duchenne muscular dystrophy treated with corticosteroids: A single‐center study of 555 patients
Alexander Zygmunt, Brenda Wong, David Moon, Paul Horn, Richard Rathbun, Joshua Lambert, Jean Bange, Irina Rybalsky, Lisa Reebals, Cuixia Tian
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引用次数: 0
Abstract
Introduction/AimsStudies have demonstrated that certain genotypes in Duchenne muscular dystrophy (DMD) have milder or more severe phenotypes. These studies included individuals treated and not treated with corticosteroids and multiple sites with potentially varying standards of care. We aimed to assess genotype–phenotype correlations for age at loss of ambulation (LoA) in a large cohort of individuals with DMD treated with corticosteroids at one center.MethodsIn this retrospective review of medical records, encounters were included for individuals diagnosed with DMD if prescribed corticosteroids, defined as daily deflazacort or prednisone or high‐dose weekend prednisone, for 12 consecutive months. Encounters were excluded if the participants were taking disease‐modifying therapy. Data were analyzed using survival analysis for LoA and Fisher's exact tests to assess the percentage of late ambulatory (>14 years old) individuals for selected genotypes.ResultsOverall, 3948 encounters from 555 individuals were included. Survival analysis showed later age at LoA for exon 44 skip amenable (p = .004), deletion exons 3–7 (p < .001) and duplication exon 2 (p = .043) cohorts and earlier age at LoA for the exon 51 skip amenable cohort (p < .001) when compared with the rest of the cohort. Individuals with deletions of exons 3–7 had significantly more late ambulatory individuals than other cohorts (75%), while those with exon 51 skip amenable deletions had significantly fewer (11.9%) compared with other cohorts.DiscussionThis confirms previous observations of genotype–phenotype correlations in DMD and enhances information for trial design and clinical management.
期刊介绍:
Muscle & Nerve is an international and interdisciplinary publication of original contributions, in both health and disease, concerning studies of the muscle, the neuromuscular junction, the peripheral motor, sensory and autonomic neurons, and the central nervous system where the behavior of the peripheral nervous system is clarified. Appearing monthly, Muscle & Nerve publishes clinical studies and clinically relevant research reports in the fields of anatomy, biochemistry, cell biology, electrophysiology and electrodiagnosis, epidemiology, genetics, immunology, pathology, pharmacology, physiology, toxicology, and virology. The Journal welcomes articles and reports on basic clinical electrophysiology and electrodiagnosis. We expedite some papers dealing with timely topics to keep up with the fast-moving pace of science, based on the referees'' recommendation.