Clinical and Pathological Phenotypes of LRP10 Variant Carriers with Dementia.
Clinical and Pathological Phenotypes of LRP10 Variant Carriers with Dementia.
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DOI：
10.3233/jad-200318
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发表时间：
2020
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影响因子：
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通讯作者：
Bonifati V
中科院分区：
文献类型：
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作者：
Vergouw LJM;Geut H;Breedveld G;Kuipers DJS;Quadri M;Netherlands Brain Bank;Rozemuller AJM;van Swieten JC;de Jong FJ;van de Berg WDJ;Bonifati V
低密度脂蛋白受体相关蛋白10基因（LRP 10）的罕见变异最近被认为与帕金森病（PD）和路易体痴呆（DLB）的病因有关。我们在一系列新的脑供体中寻找LRP 10变体，这些脑供体在尸检时患有痴呆和Lewy病理（LP），或者没有LP但患有各种其他神经退行性病理的痴呆和帕金森症。在荷兰脑库收集的233名供体中进行LRP 10的桑格测序。罕见的，可能致病的杂合LRP 10变异体存在于三名患者中：p.Gly453Ser在阿尔茨海默病（AD）/路易体病（LBD）混合患者中，p.Arg151Cys在DLB患者中，p.Gly326Asp在无LP的AD患者中。所有三名患者都有痴呆或PD的阳性家族史。罕见的LRP 10变体存在于一些患有痴呆和不同脑病理的患者中，包括DLB、混合AD/LBD和AD。这些发现表明LRP 10在广泛的神经退行性疾病谱中的作用。
Rare variants in the low-density lipoprotein receptor related protein 10 gene (LRP10) have recently been implicated in the etiology of Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). We searched for LRP10 variants in a new series of brain donors with dementia and Lewy pathology (LP) at autopsy, or dementia and parkinsonism without LP but with various other neurodegenerative pathologies. Sanger sequencing of LRP10 was performed in 233 donors collected by the Netherlands Brain Bank. Rare, possibly pathogenic heterozygous LRP10 variants were present in three patients: p.Gly453Ser in a patient with mixed Alzheimer’s disease (AD)/Lewy body disease (LBD), p.Arg151Cys in a DLB patient, and p.Gly326Asp in an AD patient without LP. All three patients had a positive family history for dementia or PD. Rare LRP10 variants are present in some patients with dementia and different brain pathologies including DLB, mixed AD/LBD, and AD. These findings suggest a role for LRP10 across a broad neurodegenerative spectrum.