Clinical outcome in 19 French and Spanish patients with valosin-containing protein myopathy associated with Paget's disease of bone and frontotemporal dementia
Clinical outcome in 19 French and Spanish patients with valosin-containing protein myopathy associated with Paget's disease of bone and frontotemporal dementia
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DOI：
10.1016/j.nmd.2009.02.012
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发表时间：
2009-05-01
影响因子：
2.8
通讯作者：
Eymard, Bruno
中科院分区：
文献类型：
--
作者：
Stojkovic, Tanya;Hammouda, El Hadi;Eymard, Bruno
我们报告了 10 个家系（19 名患者）的临床、组织学和遗传学发现，这些发现显示含缬洛辛的蛋白 (VCP) 发生突变。平均发病年龄为 42 岁。临床模式的特点是早期上肢近端受累并伴有翼状肩胛。轴向和下肢肌肉经常受到影响，而面部、眼球肌则不受影响。 10 名患者在平均病程 9 年后必须坐轮椅，6 名患者需要拐杖行走。两名患者需要机械辅助通气，七名患者肺活量下降。没有心脏受累。八名患者患有佩吉特骨病，九名患者患有认知障碍。七名患者因虚弱和呼吸困难而死亡。肌肉活检显示边缘空泡肌病。遗传分析显示错义杂合突变主要位于VCP基因的5号外显子，其中4个突变此前未曾报道。我们观察了家庭内和家庭间在严重程度、无力分布以及佩吉特病或认知障碍是否存在方面的变异性。 (C) 2009 Elsevier B.V. 保留所有权利。
We report the clinical, histological and genetic findings in 10 families (19 patients) presenting mutations in the valosin-containing protein (VCP). The mean age at onset was 42 years. The clinical pattern was characterized by an early involvement of the proximal upper limbs with scapular winging. Axial and lower limb muscles were often affected, whereas facial, oculobulbar muscles were spared. Ten patients were wheelchair bound after a mean disease course of 9 years and six patients required canes for walking. Two patients required mechanically assisted ventilation and seven patients had reduced vital capacity. There was no cardiac involvement. Paget's disease of bone was observed in eight patients and cognitive impairment in nine patients. Seven patients died as a consequence of weakness and respiratory distress. Muscle biopsy showed rimmed vacuolar myopathy. Genetic analysis revealed missense heterozygous mutations mostly located in exon 5 of the VCP gene, four of which were not previously reported. We observed intrafamilial and interfamilial variability in terms of severity, distribution of weakness and presence or not of Paget's disease or cognitive impairment. (C) 2009 Elsevier B.V. All rights reserved.