Genetic Analysis of Chinese Patients with Early-Onset Dementia Using Next-Generation Sequencing.
Genetic Analysis of Chinese Patients with Early-Onset Dementia Using Next-Generation Sequencing.
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DOI：
10.2147/cia.s271222
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发表时间：
2020
影响因子：
3.6
通讯作者：
Tao QQ
中科院分区：
文献类型：
--
作者：
Han LH;Xue YY;Zheng YC;Li XY;Lin RR;Wu ZY;Tao QQ
早发性痴呆 (EOD) 是一种相对罕见的痴呆症，患者年龄在 65 岁之前。只有少数研究在中国汉族人群中进行了 EOD 遗传学分析。由于这些疾病具有不同的遗传和临床异质性，诊断 EOD 仍然是一个挑战。本研究的目的是调查中国 EOD 患者的遗传谱和临床特征。总共招募了 49 名 EOD 患者。进行靶向下一代 (NGS) 分析以筛选与痴呆症相关的所有已知基因。通过桑格测序证实了可能的致病变异。分析EOD患者的遗传谱和临床特征。先前报道的七个致病变异（PSEN1中的p.I213T和p.W165C；APP中的p.D678N；TBK1中的c.1349_1352del；MAPT中的p.P301L和p.R406W；NOTCH3中的p.R110C）以及两个意义不确定的新变异（PSEN2中的p.P436L；鉴定出 TARDBP 中的 c.239-11G>A)。我们的研究展示了EOD患者的遗传谱和临床特征，并揭示了对EOD患者已知致病基因进行基因检测有助于做出准确的诊断。
Early-onset dementia (EOD) is a relatively uncommon form of dementia that afflicts people before age 65. Only a few studies analyzing the genetics of EOD have been performed in the Chinese Han population. Diagnosing EOD remains a challenge due to the diverse genetic and clinical heterogeneity of these diseases. The aim of this study was to investigate the genetic spectrum and clinical features of Chinese patients with EOD. A total of 49 EOD patients were recruited. Targeted next-generation (NGS) analyses were performed to screen for all of the known genes associated with dementia. Possible pathogenic variants were confirmed by performing Sanger sequencing. The genetic spectrum and clinical features of the EOD patients were analyzed. Seven previously reported pathogenic variants (p.I213T and p.W165C in PSEN1; p.D678N in APP; c.1349_1352del in TBK1; p.P301L and p.R406W in MAPT; p.R110C in NOTCH3) and two novel variants of uncertain significance (p.P436L in PSEN2; c.239-11G>A in TARDBP) were identified. Our study demonstrated the genetic spectrum and clinical features of EOD patients, and it reveals that genetic testing of known causal genes in EOD patients can help to make a precise diagnosis.