Inclusion body myopathy and frontotemporal dementia caused by a novel VCP mutation
Inclusion body myopathy and frontotemporal dementia caused by a novel VCP mutation
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DOI：
10.1016/j.neurobiolaging.2007.08.009
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发表时间：
2009-05-01
影响因子：
4.2
通讯作者：
Corti, Stefania
中科院分区：
文献类型：
--
作者：
Bersano, Anna;Del Bo, Roberto;Corti, Stefania
遗传性包涵体肌病（IBM）伴佩吉特骨病（PDB）和额颞叶痴呆（FTD）是一种罕见的常染色体显性遗传病，由含缬氨肽蛋白（VCP）基因突变引起。我们报告了一个新的杂合子VCP基因突变（R159C）在一个69岁的意大利患者表现为缓慢进行性肌无力的远端上肢和近端下肢自50岁，18年后FTD并发症。在两代家族史中未发现痴呆或肌病。在肌肉活检中观察到退行性变化和边缘空泡以及VCP和泛素阳性的细胞质和细胞核聚集体。有几个因素支持R159C VCP基因突变的致病作用：在VCP基因突变热点内，在同一密码子处发生不同的先前鉴定的致病突变，肌肉VCP蓄积的组织病理学和生化证据以及IBM和FTD的联合临床表现。这些结果表明，VCP基因调查，即使在明显的散发病例。(C)2007爱思唯尔公司All rights reserved.
Hereditary inclusion body myopathy (IBM) with Paget's disease of the bone (PDB) and frontotemporal dementia (FTD) is a rare autosomal dominant disease caused by mutations in the valosin-containing protein (VCP) gene. We report a novel heterozygous VCP gene mutation (R159C) in a 69-year-old Italian patient presenting with slowly progressive muscle weakness of the distal upper and proximal lower limbs since the age of 50 years, 18 years later FTD supervened. No dementia or myopathies were revealed in the family history covering two generations. Degenerative changes and rimmed vacuoles together with VCP- and ubiquitin-positive cytoplasmic and nuclear aggregates were observed at the muscle biopsy. Several elements support the pathogenic role of the R159C VCP gene mutation: the occurrence at the same codon of a different, previously identified pathogenic mutation within a VCP gene mutational hot-spot, the histopathological and biochemical evidence of muscle VCP accumulation and the combined clinical presentation of IBM and FTD. These findings suggest VCP gene investigation even in apparently sporadic cases. (C) 2007 Elsevier Inc. All rights reserved.