Analyses Mutations in GSN, CST3, TTR, and ITM2B Genes in Chinese Patients With Alzheimer's Disease.
Analyses Mutations in GSN, CST3, TTR, and ITM2B Genes in Chinese Patients With Alzheimer's Disease.
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分析中国阿尔茨海默病患者的 GSN、CST3、TTR 和 ITM2B 基因突变
DOI：
10.3389/fnagi.2020.581524
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发表时间：
2020
影响因子：
4.8
通讯作者：
Shen L
中科院分区：
文献类型：
--
作者：
Jiang Y;Jiao B;Liao X;Xiao X;Liu X;Shen L
淀粉样蛋白沉积是遗传性淀粉样变性（HA）和阿尔茨海默病（AD）的共同发病机制。凝溶胶蛋白（GSN）、胱抑素C（CST3）、甲状腺素运载蛋白（TTR）和整合膜蛋白2B（ITM2B）基因的突变可导致HA。但这些基因与AD之间的关系尚不清楚。对636例临床AD患者和365例正常对照者进行了GSN、CST3、TTR和ITM2B基因靶向测序（GTS）。结果，根据美国医学遗传学和基因组学学会（ACMG）指南，在5例AD患者中检测到两种新的可能致病的移码突变（GSN：c.1036delA：p.K346fs和GSN：c.8_35del：p.P3fs），这些患者的初始症状是记忆力下降，随后伴有心理和行为异常。有趣的是，K346fs突变患者出现脑β淀粉样蛋白沉积，发病早（48年），进展快，而其他4例P3fs突变患者发病晚[（平均值±标准差）：69.50 ± 5.20年]，病程长[（平均值±标准差）：9.24 ± 4.86年]。此外，我们还发现了这四个基因中的17个不确定意义（VUS）的变异。据我们所知，我们是第一个在中国队列中报告AD患者中存在GSN突变的AD表型。虽然GSN基因突变是罕见的，但它可以解释一小部分临床诊断的AD。
Amyloid protein deposition is a common mechanism of hereditary amyloidosis (HA) and Alzheimer’s disease (AD). Mutations of gelsolin (GSN), cystatin C (CST3), transthyretin (TTR), and integral membrane protein 2B (ITM2B) genes can lead to HA. But the relationship is unclear between these genes and AD. Genes targeted sequencing (GTS), including GSN, CST3, TTR, and ITM2B, was performed in a total of 636 patients with clinical AD and 365 normal controls from China. As a result, according to American College of Medical Genetics and Genomics (ACMG) guidelines, two novel likely pathogenic frame-shift mutations (GSN:c.1036delA:p.K346fs and GSN:c.8_35del:p.P3fs) were detected in five patients with AD, whose initial symptom was memory decline, accompanied with psychological and behavioral abnormalities later. Interestingly, the patient with K346fs mutation, presented cerebral β-amyloid protein deposition, had an early onset (48 years) and experienced rapid progression, while the other four patients with P3fs mutation had a late onset [(Mean ± SD): 69.50 ± 5.20 years] and a long course of illness [(Mean ± SD): 9.24 ± 4.86 years]. Besides, we also discovered 17 variants of uncertain significance (VUS) in these four genes. To our knowledge, we are the first to report AD phenotype with GSN mutations in patients with AD in the Chinese cohort. Although mutations in the GSN gene are rare, it may explain a small portion of clinically diagnosed AD.
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新型凝胶素变体是大型肾脏综合征和肾脏淀粉样变性的原因。
DOI：
10.3109/13506129.2014.891502
发表时间：
2014-06
期刊：
Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis
影响因子：
--
作者：
Efebera YA;Sturm A;Baack EC;Hofmeister CC;Satoskar A;Nadasdy T;Nadasdy G;Benson DM;Gillmore JD;Hawkins PN;Rowczenio D
通讯作者：
Rowczenio D
影响因子：
4.8
作者：
Fotinopoulou, A;Tsachaki, M;Efthimiopoulos, S
通讯作者：
Efthimiopoulos, S
DOI：
10.1073/pnas.0712197105
发表时间：
2008-02-19
影响因子：
11.1
作者：
Buxbaum, Joel N.;Ye, Zhengyi;Bartfai, Tamas
通讯作者：
Bartfai, Tamas
影响因子：
3.4
作者：
Chyra Kufova Z;Sevcikova T;Januska J;Vojta P;Boday A;Vanickova P;Filipova J;Growkova K;Jelinek T;Hajduch M;Hajek R
通讯作者：
Hajek R
影响因子：
3.4
作者：
Caress JB;Johnson JO;Abramzon YA;Hawkins GA;Gibbs JR;Sullivan EA;Chahal CS;Traynor BJ
通讯作者：
Traynor BJ