携带ABCA7基因突变的阿尔茨海默病患者的表型特征。
Phenotypic characteristics of Alzheimer patients carrying an ABCA7 mutation.
作者信息
Van den Bossche Tobi, Sleegers Kristel, Cuyvers Elise, Engelborghs Sebastiaan, Sieben Anne, De Roeck Arne, Van Cauwenberghe Caroline, Vermeulen Steven, Van den Broeck Marleen, Laureys Annelies, Peeters Karin, Mattheijssens Maria, Vandenbulcke Mathieu, Vandenberghe Rik, Martin Jean-Jacques, De Deyn Peter P, Cras Patrick, Van Broeckhoven Christine
机构信息
From the Neurodegenerative Brain Diseases Group (T.V.d.B., K.S., E.C., A.S., A.D.R., C.V.C., S.V., M.V.d.B., A.L., K.P., M.M., C.V.B.), Department of Molecular Genetics, VIB, Antwerp; Institute Born-Bunge (T.V.d.B., K.S., E.C., S.E., A.S., A.D.R., C.V.C., S.V., M.V.d.B., A.L., K.P., M.M., J.-J.M., P.P.D.D., P.C., C.V.B.), University of Antwerp; Department of Neurology (T.V.d.B., P.C.), Antwerp University Hospital, Edegem; Department of Neurology and Memory Clinic (T.V.d.B., S.E., P.P.D.D.), Hospital Netwerk Antwerp (ZNA), Middelheim and Hoge Beuken; Department of Neurology (A.S.), University Hospital Ghent and University of Ghent; Department of Neurosciences (M.V., R.V.), Faculty of Medicine, KU Leuven; Department of Old Age Psychiatry and Memory Clinic (M.V.) and Department of Neurology (R.V.), University Hospitals Leuven, Belgium; and Department of Neurology and Alzheimer Research Center (P.P.D.D.), University of Groningen and University Medical Center Groningen, the Netherlands.
出版信息
Neurology. 2016 Jun 7;86(23):2126-33. doi: 10.1212/WNL.0000000000002628. Epub 2016 Apr 1.
OBJECTIVE
To generate a clinical and pathologic phenotype of patients carrying rare loss-of-function mutations in ABCA7, identified in a Belgian Alzheimer patient cohort and in an autosomal dominant family.
METHODS
We performed a retrospective review of available data records, medical records, results of CSF analyses and neuroimaging studies, and neuropathology data.
RESULTS
The mean onset age of the mutation carriers (n = 22) was 73.4 ± 8.4 years with a wide age range of 36 (54-90) years, which was independent of APOE genotype and cerebrovascular disease. The mean disease duration was 5.7 ± 3.0 years (range 2-12 years). A positive family history was recorded for 10 carriers (45.5%). All patient carriers except one presented with memory complaints. The 4 autopsied brains showed typical immunohistochemical changes of late-onset Alzheimer disease.
CONCLUSIONS
All patients carrying a loss-of-function mutation in ABCA7 exhibited a classical Alzheimer disease phenotype, though with a striking wide onset age range, suggesting the influence of unknown modifying factors.
目的
在一个比利时阿尔茨海默病患者队列和一个常染色体显性家族中，确定携带ABCA7罕见功能丧失突变患者的临床和病理表型。
方法
我们对现有数据记录、病历、脑脊液分析结果、神经影像学研究和神经病理学数据进行了回顾性分析。
结果
突变携带者（n = 22）的平均发病年龄为73.4 ± 8.4岁，年龄范围跨度较大，为36岁（54 - 90岁），这与APOE基因型和脑血管疾病无关。平均病程为5.7 ± 3.0年（范围2 - 12年）。10名携带者（45.5%）有阳性家族史。除1名患者外，所有患者携带者均有记忆障碍主诉。4例尸检大脑显示出晚发性阿尔茨海默病典型的免疫组化变化。
结论
所有携带ABCA7功能丧失突变的患者均表现出典型的阿尔茨海默病表型，尽管发病年龄范围惊人地广泛，提示存在未知修饰因素的影响。
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