Division of Neurology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
Muscle Nerve. 2024 Nov;70(5):1053-1061. doi: 10.1002/mus.28255. Epub 2024 Sep 18.
INTRODUCTION/AIMS: Studies 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.
In 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.
Overall, 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.
This confirms previous observations of genotype-phenotype correlations in DMD and enhances information for trial design and clinical management.
简介/目的：研究表明，杜氏肌营养不良症（DMD）的某些基因型具有较轻或较重的表型。这些研究包括接受和未接受皮质类固醇治疗的个体，以及多个可能存在不同护理标准的地点。我们旨在评估在一个使用皮质类固醇治疗的大型 DMD 患者队列中，基因型与丧失行走能力（LoA）年龄的相关性。
在这项对病历的回顾性研究中，纳入了在一个中心接受皮质类固醇治疗的 DMD 患者的就诊记录，如果他们连续 12 个月每天服用地夫可特或泼尼松或大剂量周末泼尼松。如果参与者正在接受疾病修正治疗，则排除该就诊记录。使用生存分析评估 LoA 的年龄，并使用 Fisher 确切检验评估特定基因型中晚发性行走者（>14 岁）的百分比。
总共纳入了 555 名患者的 3948 次就诊记录。生存分析显示，外显子 44 跳跃可及（p = 0.004）、缺失外显子 3-7（p < 0.001）和重复外显子 2（p = 0.043）队列的 LoA 年龄较晚，而外显子 51 跳跃可及队列的 LoA 年龄较早（p < 0.001）。与其他队列相比，缺失外显子 3-7 的个体中晚期行走者明显更多（75%），而缺失外显子 51 跳跃可及的个体中晚期行走者明显更少（11.9%）。
这证实了之前在 DMD 中观察到的基因型与表型的相关性，并为试验设计和临床管理提供了更多信息。
