与早发性阿尔茨海默病相关的新型早老素 1 Y159F 序列变异。
Novel presenilin-1 Y159F sequence variant associated with early-onset Alzheimer's disease.
机构信息
Stanford Center for Memory Disorders and Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.
出版信息
Neurosci Lett. 2012 Dec 7;531(2):142-4. doi: 10.1016/j.neulet.2012.10.037. Epub 2012 Nov 2.
BACKGROUND
Mutations in the gene for presenilin-1 cause familial, early-onset Alzheimer's disease.
METHODS
We report the case of a 43-year-old woman presenting with progressive cognitive decline and a family history of early-onset dementia. Her workup included cerebrospinal fluid amyloid-beta, tau, and phospho-tau levels, as well as genetic sequencing of genes implicated in familial Alzheimer's disease.
RESULTS
Cerebrospinal fluid biomarkers were consistent with a diagnosis of Alzheimer's disease. A novel nucleotide sequence variant (A476T) was discovered in one allele for presenilin-1, corresponding to a missense tyrosine-to-phenylalanine change at codon 159 (Y159F). An affected maternal uncle carried the same allele. The sequence variant occurs in a conserved region of the gene near other previously reported mutations.
CONCLUSIONS
This novel presenilin-1 sequence variant cosegregated with early onset dementia in the proband and at least one other affected family member, and likely represents a mutation causing familial, early-onset Alzheimer's disease.
背景
早发性阿尔茨海默病的致病基因是早老素-1 基因突变。
方法
我们报告了一位 43 岁女性的病例，其表现为进行性认知能力下降，并有早发性痴呆的家族史。她的检查包括脑脊液淀粉样蛋白-β、tau 和磷酸化 tau 水平，以及家族性阿尔茨海默病相关基因的遗传测序。
结果
脑脊液生物标志物符合阿尔茨海默病的诊断。在早老素-1 的一个等位基因中发现了一种新的核苷酸序列变异（A476T），对应于密码子 159 处酪氨酸到苯丙氨酸的错义变化（Y159F）。受影响的叔公携带相同的等位基因。该序列变异发生在基因的一个保守区域，靠近其他先前报道的突变。
结论
该新型早老素-1 序列变异与先证者和至少另一位受影响的家族成员的早发性痴呆共分离，可能代表一种导致家族性早发性阿尔茨海默病的突变。
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