Gedlinske Amber M, Stephan Carrie M, Mockler Shelley R H, Laubscher Katie M, Laubenthal Karla S, Crockett Cameron D, Zimmerman M Bridget, Mathews Katherine D
From the Department of Pediatrics (A.M.G., C.M.S., C.D.C., K.D.M.) and Center for Disabilities and Development (S.R.H.M., K.M.L., K.S.L.), University of Iowa Hospitals and Clinics; and Department of Biostatistics (M.B.Z.), University of Iowa College of Public Health, Iowa City. C.D.C. is now affiliated with Washington University, St. Louis, MO.
Neurology. 2020 Oct 13;95(15):e2131-e2139. doi: 10.1212/WNL.0000000000010604. Epub 2020 Aug 6.
To test the hypothesis that we will be able to detect change in motor outcome measures over time in a cohort with mutations in .
Individuals with documented mutations were evaluated annually with a battery of established motor outcome measures including limited quantitative myometry and timed function measures. Results were analyzed using random coefficient regression to determine annual change in each measure. Due to the nonlinear progression through the lifespan of the study participants, pediatric (<19 years) and adult (≥19 years) cohorts were analyzed separately. Effect of genotype was evaluated in each cohort.
Sixty-nine participants (30 pediatric, 44 adult) with at least 2 evaluations were included. There was a small but statistically significant decline in timed motor function measures in both pediatric and adult cohorts. Genotype significantly affected rate of decline in the pediatric but not the adult cohort. Some pediatric patients who are homozygous for the c.826C>A mutation showed improving motor performance in adolescence. Performance on the 10-meter walk/run was highly correlated with other timed function tests.
There is a slow annual decline in motor function in adults with mutations that can be detected with standard motor outcome measures, while the results in the pediatric population were more variable and affected by genotype. Overall, these analyses provide a framework for development of future clinical trials. The dystroglycanopathies natural history study (Clinical Trial Readiness for the Dystroglycanopathies) may be found on clinicaltrials.gov (NCT00313677).
检验以下假设，即我们能够在一个携带[具体基因名称]突变的队列中检测到运动结果指标随时间的变化。
对有记录的[具体基因名称]突变个体每年进行一系列既定的运动结果评估，包括有限的定量肌动测量法和定时功能测量。使用随机系数回归分析结果，以确定每个指标的年度变化。由于研究参与者在整个生命周期中的进展是非线性的，因此分别分析了儿科（<19岁）和成人（≥19岁）队列。在每个队列中评估基因型的影响。
纳入了69名至少接受过2次评估的参与者（30名儿科患者，44名成人）。儿科和成人队列的定时运动功能测量均有轻微但具有统计学意义的下降。基因型对儿科队列的下降速率有显著影响，但对成人队列没有影响。一些c.826C>A突变纯合的儿科患者在青春期运动表现有所改善。10米步行/跑步的表现与其他定时功能测试高度相关。
携带[具体基因名称]突变的成年人运动功能每年有缓慢下降，可通过标准运动结果指标检测到，而儿科人群的结果更具变异性且受基因型影响。总体而言，这些分析为未来临床试验的开展提供了框架。糖基化肌营养不良自然史研究（糖基化肌营养不良的临床试验准备）可在clinicaltrials.gov（NCT00313677）上找到。
