RT期刊文章SR电子T1临床和影像特征的早发性老年痴呆症SORL1废话变体(p5 - 6.005)摩根富林明神经病学神经学乔FD Lippincott Williams &威尔金斯SP 4701 10.1212 / WNL。首页0000000000204168签证官100 17补充2 A1康纳黄素A1 Christine Cliatt布朗A1 Jared巴特尔A1艾米丽Spoth A1 Satoshi Minoshima A1保罗·莫雷蒂年2023 UL //www.ez-admanager.com/content/100/17_Supplement_2/4701.abs首页tract AB目的:描述的早发性阿尔茨海默病(AD)的载波SORL1废话与痴呆家族史的变体,临床进展缓慢,非常微妙的发现指出正。背景:SORL1基因编码sortilin-related受体参与β淀粉样蛋白溶酶体降解和间隙。SORL1基因变异与AD风险增加有关联或高渗透的疾病谱系。设置的痴呆家族史,这个基因可能导致广告起着重要的作用。设计/方法:56岁男性被评估的13年历史进步的认知和记忆衰退。他与复杂困难IADLs(理财、交通、药物)与基本ADLs虽然保存性能。有一个在他父亲痴呆家族史,发病年龄在65年,在他的兄弟和认知减退,在他的50年代早期症状出现。结果:神经心理学测试演示了在语言学习和记忆障碍,视觉记忆和相对疲软类别流利,虽然否则高性能在多个其他领域。摄影显示双边内侧颞代谢减退和后扣带代谢减退。核磁共振大脑显示只有细微的颞叶萎缩。 Genetic testing revealed a pathogenic nonsense mutation in the SORL1 gene, c.862del (p.Glu288Lysfs*5). This variant is absent from population databases and is predicted to result in absent or disrupted protein.Conclusions: This SORL1 variant is suspected to cause AD in this patient with slowly progressive Early-Onset AD and unusually subtle imaging findings. Studies suggest that frameshift and nonsense variants leading to loss of protein function are highly penetrant, lead to an earlier age of onset, and may confer a twelve-fold increased risk of AD. Further research is needed to determine the risk of AD, the rate of progression, and the typical imaging features in patients with SORL1 variants.Disclosure: Dr. Flavin has nothing to disclose. Dr. Cliatt Brown has nothing to disclose. Jared Bartell, MD has nothing to disclose. Ms. Spoth has stock in Applied Genetic Technologies Corporation. Ms. Spoth has stock in MeiraGTx Holdings. Ms. Spoth has stock in Ocugen. Ms. Spoth has stock in PTC Therapeutics. Satoshi Minoshima has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Hamamatsu Photonics. The institution of Satoshi Minoshima has received research support from Nihon Medi-physics. The institution of Satoshi Minoshima has received research support from Fujifilm. The institution of an immediate family member of Dr. Moretti has received research support from NIH. The institution of an immediate family member of Dr. Moretti has received research support from VHA. The institution of an immediate family member of Dr. Moretti has received research support from DOD.

map