Nasu-Hakola disease (polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy - PLOSL): A dementia associated with bone cystic lesions. From clinical to genetic and molecular aspects
Nasu-Hakola disease (polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy - PLOSL): A dementia associated with bone cystic lesions. From clinical to genetic and molecular aspects
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DOI：
10.1023/b:cemn.0000012721.08168.ee
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发表时间：
2004-02-01
影响因子：
4
通讯作者：
Sakamoto, AC
中科院分区：
文献类型：
--
作者：
Bianchin, MM;Capella, HM;Sakamoto, AC
作者回顾了Nasu-Hakola病(伴有硬化性白质脑病的多囊性脂膜骨质增生症)的临床、放射学、电生理、病理学和分子方面的研究进展。Nasu-Hakola病是一种独特的疾病，其特征是多发性骨囊肿与一种特殊形式的神经变性有关，这种疾病通常会导致痴呆和性早逝，通常发生在人的第五个十年。诊断可以根据临床和放射学表现来确定。最近，对受影响家庭的分子分析发现了DAP12(TYROBP)或TREM2基因的突变，这提供了一个有趣的例子，说明多亚单位受体复合体的两个不同亚基的突变如何导致相同的人类疾病表型。PLOSL与DAP12或TREM2基因突变的关联导致了对受影响个体的诊断有所改善。此外，DAP12/TREM2信号通路在人类小胶质细胞和破骨细胞中的可能作用才刚刚开始阐明。这里讨论了这一特殊信号通路的某些方面。
The authors review the clinical, radiological, electrophysiological, pathological, and molecular aspects of Nasu - Hakola disease ( polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy or PLOSL). Nasu-Hakola disease is a unique disease characterized by multiple bone cysts associated with a peculiar form of neurodegeneration that leads to dementia and precocious death usually during the fifth decade of life. The diagnosis can be established on the basis of clinical and radiological findings. Recently, molecular analysis of affected families revealed mutations in the DAP12 ( TYROBP) or TREM2 genes, providing an interesting example how mutations in two different subunits of a multi-subunit receptor complex result in an identical human disease phenotype. The association of PLOSL with mutations in the DAP12 or TREM2 genes has led to improved diagnosis of affected individuals. Also, the possible roles of the DAP12/TREM2 signaling pathway in microglia and osteoclasts in humans are just beginning to be elucidated. Some aspects of this peculiar signaling pathway are discussed here.