1型强直性肌营养不良症中可变重复序列中断与临床结局之间的关联
Associations Between Variant Repeat Interruptions and Clinical Outcomes in Myotonic Dystrophy Type 1.
作者信息
Wenninger Stephan, Cumming Sarah A, Gutschmidt Kristina, Okkersen Kees, Jimenez-Moreno Aura Cecilia, Daidj Ferroudja, Lochmüller Hanns, Hogarth Fiona, Knoop Hans, Bassez Guillaume, Monckton Darren G, van Engelen Baziel G M, Schoser Benedikt
机构信息
Department of Neurology (S.W., K.G., B.S.), Friedrich-Baur-Institute, Ludwig-Maximilians-Universität München, Germany; Institute of Molecular, Cell and Systems Biology (S.A.C., D.G.M.), University of Glasgow, United Kingdom; Department of Neurology (K.O., B.G.M.v.E.), Radboud University, Nijmegen, The Netherlands; Institute of Genetic Medicine (A.C.J.-M.), Institute for Ageing and Health, Newcastle University, United Kingdom; Neuromuscular Reference Centre (F.D., G.B.), Assistance Publique-Hôpitaux de Paris, France; Department of Neuropediatrics and Muscle Disorders (H.L.), University of Freiburg, Breisgau, Germany; Center for Genomic Regulation (H.L.), Barcelona Institute of Science and Technology, Spain; Tayside Clinical Trials Unit (F.H.), The University of Dundee, United Kingdom; and Department of Medical Psychology (H.K.), Amsterdam University Medical Centers, University of Amsterdam, Amsterdam Public Health Research Institute, Amsterdam, The Netherlands.
出版信息
Neurol Genet. 2021 Mar 9;7(2):e572. doi: 10.1212/NXG.0000000000000572. eCollection 2021 Apr.
OBJECTIVE
To assess the association between variant repeat (VR) interruptions in patients with myotonic dystrophy type 1 (DM1) and clinical symptoms and outcome measures after cognitive behavioral therapy (CBT) intervention.
METHODS
Adult patients with DM1 were recruited within the OPTIMISTIC trial (NCT02118779). Disease-related history, current clinical symptoms and comorbidities, functional assessments, and disease- and health-related questionnaires were obtained at baseline and after 5 and 10 months. After genetic analysis, we assessed the association between the presence of VR interruptions and clinical symptoms' long-term outcomes and compared the effects of CBT in patients with and without VR interruptions. Core trial outcome measures analyzed were: 6-minute walking test, DM1-Activ-C, Checklist Individual Strength Fatigue Score, Myotonic Dystrophy Health Index, McGill-Pain questionnaire, and Beck Depression inventory-fast screen. Blood samples for DNA testing were obtained at the baseline visit for determining CTG length and detection of VR interruptions.
RESULTS
VR interruptions were detectable in 21/250 patients (8.4%)-12 were assigned to the standard-of-care group (control group) and 9 to the CBT group. Patients with VR interruptions were significantly older when the first medical problem occurred and had a significantly shorter disease duration at baseline. We found a tendency toward a milder disease severity in patients with VR interruptions, especially in ventilation status, mobility, and cardiac symptoms. Changes in clinical outcome measures after CBT were not associated with the presence of VR interruptions.
CONCLUSIONS
The presence of VR interruptions is associated with a later onset of the disease and a milder phenotype. However, based on the OPTIMISTIC trial data, the presence of VR interruptions was not associated with significant changes on outcome measures after CBT intervention.
TRIAL REGISTRATION INFORMATION
ClinicalTrials.gov NCT02118779.
目的
评估1型强直性肌营养不良（DM1）患者中的变异重复（VR）中断与认知行为疗法（CBT）干预后的临床症状及结局指标之间的关联。
方法
在OPTIMISTIC试验（NCT02118779）中招募成年DM1患者。在基线、5个月和10个月后获取疾病相关病史、当前临床症状和合并症、功能评估以及与疾病和健康相关的问卷。经过基因分析后，我们评估了VR中断的存在与临床症状长期结局之间的关联，并比较了CBT对有和没有VR中断患者的影响。分析的核心试验结局指标包括：6分钟步行试验、DM1-Activ-C、个人力量疲劳检查表评分、强直性肌营养不良健康指数、麦吉尔疼痛问卷和贝克抑郁量表快速筛查。在基线访视时采集用于DNA检测的血样，以确定CTG长度并检测VR中断。
结果
在250名患者中有21名（8.4%）可检测到VR中断——12名被分配到标准治疗组（对照组），9名被分配到CBT组。首次出现医疗问题时，有VR中断的患者年龄显著更大，且基线时疾病持续时间显著更短。我们发现有VR中断的患者疾病严重程度有趋于较轻的倾向，尤其是在通气状态、活动能力和心脏症状方面。CBT后临床结局指标的变化与VR中断的存在无关。
结论
VR中断的存在与疾病较晚发病和较轻的表型相关。然而，根据OPTIMISTIC试验数据，VR中断的存在与CBT干预后结局指标的显著变化无关。
试验注册信息
ClinicalTrials.gov NCT02118779
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