Identification of a Novel Hemizygous SQSTM1 Nonsense Mutation in Atypical Behavioral Variant Frontotemporal Dementia.
Identification of a Novel Hemizygous SQSTM1 Nonsense Mutation in Atypical Behavioral Variant Frontotemporal Dementia.
复制标题
非典型行为变异额颞叶痴呆中新型半合子 SQSTM1 无义突变的鉴定
DOI：
10.3389/fnagi.2018.00026
复制
发表时间：
2018
影响因子：
4.8
通讯作者：
Li X
中科院分区：
文献类型：
--
作者：
Sun L;Rong Z;Li W;Zheng H;Xiao S;Li X
额颞叶痴呆包括一系列神经退行性疾病。SQSTM 1编码p62蛋白，在FTD的发病机制中起重要作用。在这里，我们报告了一例SQSTM 1突变S224 X的女性患者，她最初表现出记忆力下降，轻度人格改变，以及磁共振成像（MRI）中额叶/颞叶的轻微萎缩，年龄为59岁。基因检测显示SQSTM 1基因（S224 X）的无义突变，导致蛋白质合成提前终止，预测截短的蛋白质比正常蛋白质短217个氨基酸。此外，在过表达SQSTM 1 S224 X突变体的HEK-293 T细胞中，既未检测到完整的SQSTM 1蛋白，也未检测到截短的SQSTM 1蛋白。我们检测了患者外周血白细胞样本中的SQSTM 1 cDNA，未检测到其突变。定量PCR检测结果显示，与5名痴呆对照相比，患者外周血白细胞中SQSTM 1 mRNA的水平显著降低。我们的研究结果确定了一个新的致病性SQSTM 1 S224 X突变的非典型FTD患者伴随SQSTM 1/p62蛋白表达的损失可能是由于SQSTM 1基因单倍不足。
Frontotemporal dementia includes a large spectrum of neurodegenerative disorders. SQSTM1, coding for p62 protein, plays a vital role in the pathogenesis of FTD. Here, we report a case of a female patient with SQSTM1 mutation S224X, who was 59 years old when she initially exhibited memory decline, mild personality changes, and subtle atrophy of frontal/temporal lobes in magnetic resonance imaging (MRI). Genetic testing revealed a nonsense mutation of the SQSTM1 gene (S224X), resulting in premature termination of protein synthesis and a predicted truncated protein 217 amino acids shorter than the normal protein. Moreover, neither intact nor truncated SQSTM1 proteins was detectable in SQSTM1 S224X mutant overexpressing HEK-293T cells. We assayed for SQSTM1 cDNA in samples from the patient's peripheral leucocytes, and did not detect its mutation. The test of quantitative PCR showed significant decreased level of SQSTM1 mRNA from peripheral leucocytes of the patient compared to five dementia controls. Our results identify a novel pathogenic SQSTM1 S224X mutation in an atypical FTD patient accompanied with loss of SQSTM1/p62 protein expression probably due to SQSTM1 gene haploinsufficiency.
登录
查看更多内容
影响因子：
14.9
作者：
López-Perrote A;Castaño R;Melero R;Zamarro T;Kurosawa H;Ohnishi T;Uchiyama A;Aoyagi K;Buchwald G;Kataoka N;Yamashita A;Llorca O
通讯作者：
Llorca O
DOI：
10.3233/jad-141512
发表时间：
2015
期刊：
Journal of Alzheimer's disease : JAD
影响因子：
--
作者：
Boutoleau-Bretonnière C;Camuzat A;Le Ber I;Bouya-Ahmed K;Guerreiro R;Deruet AL;Evrard C;Bras J;Lamy E;Auffray-Calvier E;Pallardy A;Hardy J;Brice A;Derkinderen P;Vercelletto M
通讯作者：
Vercelletto M
影响因子：
2.4
作者：
Ji Y;Liu M;Huo YR;Liu S;Shi Z;Liu S;Wisniewski T;Wang J
通讯作者：
Wang J
影响因子：
12.7
作者：
van der Zee J;Van Langenhove T;Kovacs GG;Dillen L;Deschamps W;Engelborghs S;Matěj R;Vandenbulcke M;Sieben A;Dermaut B;Smets K;Van Damme P;Merlin C;Laureys A;Van Den Broeck M;Mattheijssens M;Peeters K;Benussi L;Binetti G;Ghidoni R;Borroni B;Padovani A;Archetti S;Pastor P;Razquin C;Ortega-Cubero S;Hernández I;Boada M;Ruiz A;de Mendonça A;Miltenberger-Miltényi G;do Couto FS;Sorbi S;Nacmias B;Bagnoli S;Graff C;Chiang HH;Thonberg H;Perneczky R;Diehl-Schmid J;Alexopoulos P;Frisoni GB;Bonvicini C;Synofzik M;Maetzler W;vom Hagen JM;Schöls L;Haack TB;Strom TM;Prokisch H;Dols-Icardo O;Clarimón J;Lleó A;Santana I;Almeida MR;Santiago B;Heneka MT;Jessen F;Ramirez A;Sanchez-Valle R;Llado A;Gelpi E;Sarafov S;Tournev I;Jordanova A;Parobkova E;Fabrizi GM;Testi S;Salmon E;Ströbel T;Santens P;Robberecht W;De Jonghe P;Martin JJ;Cras P;Vandenberghe R;De Deyn PP;Cruts M;Sleegers K;Van Broeckhoven C
通讯作者：
Van Broeckhoven C
影响因子：
2.3
作者：
Kovacs, Gabor G.;van der Zee, Julie;Matej, Radoslav
通讯作者：
Matej, Radoslav