Confirming Pathogenicity of the F386L PSEN1 Variant in a South Asian Family With Early-Onset Alzheimer Disease.
Confirming Pathogenicity of the F386L PSEN1 Variant in a South Asian Family With Early-Onset Alzheimer Disease.
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DOI：
10.1212/nxg.0000000000000647
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发表时间：
2022-03
期刊：
影响因子：
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通讯作者：
Greicius MD
中科院分区：
文献类型：
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作者：
Eger SJ;Le Guen Y;Khan RR;Hall JN;Kennedy G;Zaharchuk G;Couthouis J;Brooks WS;Velakoulis D;Napolioni V;Belloy ME;Dalgard CL;Mormino EC;Gitler AD;Greicius MD
在1个日本家族中报告了F386 L PSEN 1变体，临床信息有限。我们的目的是通过证明F386 L与早发性阿尔茨海默病（AD）分离来证明F386 L是致病的。一个南亚家庭的八个人提供了DNA进行基因检测，并接受了神经系统检查。女性先证者在45岁时被诊断为AD，并在49岁时死亡。她的CSF生物标志物特征与AD一致，并且她的氟倍他滨PET扫描为淀粉样蛋白阳性，纹状体中有高摄取。她的MRI显示没有明显的白色病变。她受影响的亲属的发病年龄范围为38-57岁，成像和生物标志物特征与她相似。本文中的结果与先前的报告一起证实了F386 L的致病性。此外，我们的研究强调了研究来自代表性不足人群的家族的重要性，以识别或确认可能特定于某些遗传祖先的罕见变异的致病性。
The F386L PSEN1 variant has been reported in 1 Japanese family with limited clinical information. We aimed to prove that F386L is pathogenic by demonstrating that it segregates with early-onset Alzheimer disease (AD). Eight individuals in a South Asian family provided DNA for genetic testing and underwent a neurologic examination. The female proband was diagnosed with AD at age 45 years and died at age 49 years. She had a CSF biomarker profile consistent with AD, and her florbetaben PET scan was amyloid positive with high uptake in the striatum. Her MRI showed no prominent white matter disease. Her affected relatives had an age at onset range of 38–57 years and had imaging and biomarker profiles similar to hers. The results presented here, in conjunction with the prior report, confirm the pathogenicity of F386L. Furthermore, our study highlights the importance of studying families from underrepresented populations to identify or confirm the pathogenicity of rare variants that may be specific to certain genetic ancestries.