180p不同基因型杜氏肌营养不良患者下肢和上肢运动功能下降的研究

IF 2.8 4区 医学 Q2 CLINICAL NEUROLOGY
E. Fleerakkers , J. Broos , R. Hoek , Y. Krom , M. Michaels , H. Kan , H. van Duyvenvoorde , M. van der Holst , E. Niks
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引用次数: 0

摘要

杜氏肌营养不良(DMD)患者下肢功能丧失先于手臂功能丧失。此外,丧失活动能力(LoA)作为临床里程碑的风险与特定基因型相关。然而,目前尚不清楚失去下肢和上肢里程碑的时间是否相关,以及相同的基因型是否与失去作为上肢主要里程碑的手到口运动(LoHM)有关。莱顿大学医学中心DMD患者的门诊临床数据来自荷兰营养不良症数据库。根据致病变异的位置(近端≤外显子44 vs远端≥外显子45)和外显子跳过资格(可跳过外显子44、45、51或53)对患者进行分类。LoA年龄与LoHM(定义为PUL 2.0入学分数<;3)之间的关系采用Spearman相关检验。Kaplan-Meier曲线用于可视化LoA和LoHM的时间。采用log-rank检验比较不同亚组间LoA和LoHM的时间。共纳入120例患者(平均基线年龄:9.9岁,SD 7.35;平均随访时间:6.64岁,SD 4.37;平均7.4次就诊/患者)。80例患者达到LoA(平均年龄10.7岁(SD 2.05)), 41例患者达到LoHM(平均年龄18.1岁(SD 5.88))。LoA与LoHM呈正相关(r=0.421, p=0.003)。51外显子可跳过患者的平均LoA时间比44外显子患者早2.9年,但无统计学意义(p=0.186)。然而,在到达LoHM的时间上观察到显著差异,外显子51可跳过的患者到达LoHM的平均时间比外显子44的患者早6.6年(p=0.017)。在其他亚组中没有观察到显著差异。我们的数据显示,更早的LoA与更早的LoHM相关,并且适合51外显子跳过的组比符合44外显子跳过的组更早地经历LoHM。这些结果可作为上肢功能的预测指标,为临床监测和决策提供支持。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
180PExploring motor function decline in lower and upper extremity function across different genotypes in Duchenne muscular dystrophy
In patients with Duchenne muscular dystrophy (DMD) loss of lower limb function precedes prior to arm function. Additionally, the risk of losing ambulation (LoA) as a clinical milestone is associated with specific genotypes. However, it is less clear if the timing of losing lower and upper limb milestones is related and if the same genotypes are related to loss of hand-to-mouth movement (LoHM) as major upper limb milestone. Outpatient clinical data from DMD patients at Leiden Univ Med Center was obtained from the Dutch Dystrophinopathy Database. Patients were categorized by location of the pathogenic variant (proximal ≤exon 44 vs. distal ≥exon 45) and by exon skipping eligibility (amenable to skipping of exon 44, 45, 51, or 53). The association between age at LoA and LoHM (defined as PUL 2.0 entry score <3) was tested using Spearman correlation. Kaplan-Meier curves were used to visualize the time to LoA and LoHM. Timing of LoA and LoHM were compared across different subgroups using log-rank tests. A total of 120 patients were included (mean baseline age: 9.9 y, SD 7.35; mean follow-up: 6.64 y, SD 4.37; average 7.4 visits/patient). Eighty patients reached LoA (mean age at LoA 10.7 y (SD 2.05)) and 41 LoHM (mean age at LoHM 18.1 y (SD 5.88)). LoA and LoHM were moderately correlated (r=0.421, p=0.003). The mean time to LoA was 2.9 years earlier in exon 51 skippable patients than in exon 44, without reaching statistical significance (p=0.186). However, a significant difference was observed in time to LoHM, the mean time to LoHM was 6.6 years earlier in exon 51 skippable patients than in exon 44 (p=0.017). In the other subgroups no significant differences were observed. Our data show that earlier LoA is associated with earlier LoHM and that the group amenable to exon 51 skipping experiences earlier LoHM than those eligible for exon 44 skipping. These results may serve as a predictive marker for upper limb function and support clinical monitoring and decision-making.
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来源期刊
Neuromuscular Disorders
Neuromuscular Disorders 医学-临床神经学
CiteScore
4.60
自引率
3.60%
发文量
543
审稿时长
53 days
期刊介绍: This international, multidisciplinary journal covers all aspects of neuromuscular disorders in childhood and adult life (including the muscular dystrophies, spinal muscular atrophies, hereditary neuropathies, congenital myopathies, myasthenias, myotonic syndromes, metabolic myopathies and inflammatory myopathies). The Editors welcome original articles from all areas of the field: • Clinical aspects, such as new clinical entities, case studies of interest, treatment, management and rehabilitation (including biomechanics, orthotic design and surgery). • Basic scientific studies of relevance to the clinical syndromes, including advances in the fields of molecular biology and genetics. • Studies of animal models relevant to the human diseases. The journal is aimed at a wide range of clinicians, pathologists, associated paramedical professionals and clinical and basic scientists with an interest in the study of neuromuscular disorders.
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