纵向CINRG贝克尔自然历史研究的发现。

IF 3.2 4区 医学 Q2 CLINICAL NEUROLOGY
Paula R Clemens, Heather Gordish-Dressman, Gabriela Niizawa, Ksenija Gorni, Michela Guglieri, Anne M Connolly, Matthew Wicklund, Tulio Bertorini, Jean Mah, Mathula Thangarajh, Edward C Smith, Nancy L Kuntz, Craig M McDonald, Erik Henricson, S Upadhyayula, Barry Byrne, Georgios Manousakis, Amy Harper, Susan Iannaccone, Utkarsh J Dang
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引用次数: 0

摘要

背景:贝克肌营养不良症是一种x连锁的遗传性疾病,引起骨骼肌和心肌的进行性变性,具有广泛可变的表型。目的:对经证实的贝克肌营养不良症患者提供的3年纵向前瞻性数据集进行分析,以表征该疾病的自然史。更好地了解自然历史对严格的治疗试验至关重要。方法:83例贝克肌营养不良患者(基线年龄5-75岁)随访3年,每年进行一次评估。本文分析了肌肉和肺功能的结果。进行年龄分层统计分析和建模,分析横截面数据、事件发生时间数据和纵向数据,以表征这些临床结果。结果:肌营养不良蛋白外显子45-47和45-48缺失突变最为常见。亚组分析显示,基线时运动结果的两两相关性大于这些结果与年龄的相关性。与18岁以下的人相比,成年人的结果之间的相关性更强。通过横断面分箱分析,在北极星门诊评估中发现了天花板效应,但在其他功能结果中没有。纵向分析显示,在整个生命周期中,预测的强迫肺活量百分比下降。运动功能结果的中位功能在儿童期和青春期相对稳定或改善,之后随着年龄的增长功能下降。结论:贝克肌营养不良症的临床表型存在显著的异质性,结果的进展是可变的。疾病进展主要表现在成年期。对贝克尔自然历史数据集的纵向分析揭示了临床试验设计的启示。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Findings from the Longitudinal CINRG Becker Natural History Study.

Background: Becker muscular dystrophy is an X-linked, genetic disorder causing progressive degeneration of skeletal and cardiac muscle, with a widely variable phenotype.

Objective: A 3-year, longitudinal, prospective dataset contributed by patients with confirmed Becker muscular dystrophy was analyzed to characterize the natural history of this disorder. A better understanding of the natural history is crucial to rigorous therapeutic trials.

Methods: A cohort of 83 patients with Becker muscular dystrophy (5-75 years at baseline) were followed for up to 3 years with annual assessments. Muscle and pulmonary function outcomes were analyzed herein. Age-stratified statistical analysis and modeling were conducted to analyze cross-sectional data, time-to-event data, and longitudinal data to characterize these clinical outcomes.

Results: Deletion mutations of dystrophin exons 45-47 or 45-48 were most common. Subgroup analysis showed greater pairwise association between motor outcomes at baseline than association between these outcomes and age. Stronger correlations between outcomes for adults than for those under 18 years were also observed. Using cross-sectional binning analysis, a ceiling effect was seen for North Star Ambulatory Assessment but not for other functional outcomes. Longitudinal analysis showed a decline in percentage predicted forced vital capacity over the life span. There was relative stability or improved median function for motor functional outcomes through childhood and adolescence and decreasing function with age thereafter.

Conclusions: There is variable progression of outcomes resulting in significant heterogeneity of the clinical phenotype of Becker muscular dystrophy. Disease progression is largely manifest in adulthood. There are implications for clinical trial design revealed by this longitudinal analysis of a Becker natural history dataset.

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来源期刊
Journal of neuromuscular diseases
Journal of neuromuscular diseases Medicine-Neurology (clinical)
CiteScore
5.10
自引率
6.10%
发文量
102
期刊介绍: The Journal of Neuromuscular Diseases aims to facilitate progress in understanding the molecular genetics/correlates, pathogenesis, pharmacology, diagnosis and treatment of acquired and genetic neuromuscular diseases (including muscular dystrophy, myasthenia gravis, spinal muscular atrophy, neuropathies, myopathies, myotonias and myositis). The journal publishes research reports, reviews, short communications, letters-to-the-editor, and will consider research that has negative findings. The journal is dedicated to providing an open forum for original research in basic science, translational and clinical research that will improve our fundamental understanding and lead to effective treatments of neuromuscular diseases.
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