CMT subtypes and disease burden in patients enrolled in the Inherited Neuropathies Consortium natural history study: a cross-sectional analysis.
CMT subtypes and disease burden in patients enrolled in the Inherited Neuropathies Consortium natural history study: a cross-sectional analysis.
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DOI：
10.1136/jnnp-2014-308826
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发表时间：
2015-08
期刊：
影响因子：
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通讯作者：
Inherited Neuropathies Consortium
中科院分区：
文献类型：
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作者：
Fridman V;Bundy B;Reilly MM;Pareyson D;Bacon C;Burns J;Day J;Feely S;Finkel RS;Grider T;Kirk CA;Herrmann DN;Laurá M;Li J;Lloyd T;Sumner CJ;Muntoni F;Piscosquito G;Ramchandren S;Shy R;Siskind CE;Yum SW;Moroni I;Pagliano E;Zuchner S;Scherer SS;Shy ME;Inherited Neuropathies Consortium
国际遗传性神经病联盟 (INC) 成立的目的是获得腓骨肌萎缩症 (CMT) 患者急需的自然史数据。我们分析了 INC 患者的临床和遗传数据，以确定 CMT 亚型的分布以及与其相关的临床损伤。我们分析了在 13 个 INC 中心评估的 1652 名患者的数据。确定了 CMT 亚型的分布和致病基因突变。所有突变的疾病负担均通过 CMT 神经病变评分 (CMTNS) 和 CMT 检查评分 (CMTES) 进行评估。 1652 名患者中有 997 名（60.4%）接受了基因诊断。最常见的 CMT 亚型是 CMT1A/PMP22 重复、CMT1X/GJB1 突变、CMT2A/MFN2 突变、CMT1B/MPZ 突变以及导致压力性麻痹/PMP22 缺失的遗传性神经病。这五种 CMT 亚型占所有基因确认突变的 89.2%。某些但并非所有亚型的平均 CMTNS 与之前报道的相似。我们的研究结果证实，已经招募了大量具有代表性的各种 CMT 亚型的患者，并且实现分子诊断的频率和 CMT 亚型的分布反映了之前报道的情况。严重程度的衡量标准与较小系列的结果相似，但不相同。这项研究证实，可以在国际中心之间以统一的方式评估患者，这对于计划的自然历史研究和未来的临床试验至关重要。这些数据将为 CMT 纵向研究提供代表性基线。 ID 号 NCT01193075。
The international Inherited Neuropathy Consortium (INC) was created with the goal of obtaining much needed natural history data for patients with Charcot-Marie-Tooth (CMT) disease. We analysed clinical and genetic data from patients in the INC to determine the distribution of CMT subtypes and the clinical impairment associated with them. We analysed data from 1652 patients evaluated at 13 INC centres. The distribution of CMT subtypes and pathogenic genetic mutations were determined. The disease burden of all the mutations was assessed by the CMT Neuropathy Score (CMTNS) and CMT Examination Score (CMTES). 997 of the 1652 patients (60.4%) received a genetic diagnosis. The most common CMT subtypes were CMT1A/PMP22 duplication, CMT1X/GJB1 mutation, CMT2A/MFN2 mutation, CMT1B/MPZ mutation, and hereditary neuropathy with liability to pressure palsy/PMP22 deletion. These five subtypes of CMT accounted for 89.2% of all genetically confirmed mutations. Mean CMTNS for some but not all subtypes were similar to those previously reported. Our findings confirm that large numbers of patients with a representative variety of CMT subtypes have been enrolled and that the frequency of achieving a molecular diagnosis and distribution of the CMT subtypes reflects those previously reported. Measures of severity are similar, though not identical, to results from smaller series. This study confirms that it is possible to assess patients in a uniform way between international centres, which is critical for the planned natural history study and future clinical trials. These data will provide a representative baseline for longitudinal studies of CMT. ID number NCT01193075.