Clinical features of facioscapulohumeral muscular dystrophy 2
Clinical features of facioscapulohumeral muscular dystrophy 2
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DOI：
10.1212/wnl.0b013e3181f96175
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发表时间：
2010-10-26
期刊：
影响因子：
9.9
通讯作者：
Tawil, R.
中科院分区：
文献类型：
--
作者：
de Greef, J. C.;Lemmers, R. J. L. F.;Tawil, R.
目的：面肩肱型肌营养不良症（FSHD）患者中约有5%的患者染色体4 q35上没有D4 Z4重复收缩。这些患者被称为FSHD 2患者，显示出与D4 Z4收缩（FSHD 1）患者相似的D4 Z4重复序列处的DNA甲基化和异染色质标记物的丢失。这种共性表明D4 Z4染色质结构的变化使FSHD 1和FSHD 2统一。我们的研究的目的是严格评估FSHD 2患者的临床特征，以确定这些患者是否与FSHD 1表型相同，并建立（表型）基因型对phenotype.Methods的影响：本横断面研究研究了33例FSHD 2患者从27个家庭，迄今为止描述的最大队列。使用标准化临床评估表对所有患者进行临床评估。结果：FSHD 2与FSHD 1的临床表现一致。值得注意的差异包括散发病例的发生率较高（67%），并且在FSHD 2中疾病严重程度没有性别差异。总体而言，FSHD 2中的平均疾病严重程度与FSHD 1中报告的相似，并且不受D4 Z4重复大小的影响。在FSHD 2中，低甲基化程度对疾病严重程度的影响很小，observed.Conclusions：在临床上，FSHD 2患者与FSHD 1患者难以区分。目前的数据表明，FSHD 1和FSHD 2是相同的病理生理过程的结果。神经病学（R）2010;75：1548-1554
Objective: In some 5% of patients with facioscapulohumeral muscular dystrophy (FSHD), no D4Z4 repeat contraction on chromosome 4q35 is observed. Such patients, termed patients with FSHD2, show loss of DNA methylation and heterochromatin markers at the D4Z4 repeat that are similar to patients with D4Z4 contractions (FSHD1). This commonality suggests that a change in D4Z4 chromatin structure unifies FSHD1 and FSHD2. The aim of our study was to critically evaluate the clinical features in patients with FSHD2 in order to establish whether these patients are phenotypically identical to FSHD1 and to establish the effects of the (epi-) genotype on the phenotype.Methods: This cross-sectional study studied 33 patients with FSHD2 from 27 families, the largest cohort described to date. All patients were clinically assessed using a standardized clinical evaluation form. Genotype analysis was performed by pulsed field gel electrophoresis and PCR; D4Z4 methylation was studied by methylation-sensitive Southern blot analysis.Results: FSHD2 is identical to FSHD1 in its clinical presentation. Notable differences include a higher incidence (67%) of sporadic cases and the absence of gender differences in disease severity in FSHD2. Overall, average disease severity in FSHD2 was similar to that reported in FSHD1 and was not influenced by D4Z4 repeat size. In FSHD2, a small effect of the degree of hypomethylation on disease severity was observed.Conclusions: Clinically, patients with FSHD2 are indistinguishable from patients with FSHD1. The present data suggest that FSHD1 and FSHD2 are the result of the same pathophysiologic process. Neurology (R) 2010;75:1548-1554