The role of MAPT gene in Chinese dementia patients: a P301L pedigree study and brief literature review.
The role of MAPT gene in Chinese dementia patients: a P301L pedigree study and brief literature review.
复制标题
MAPT基因在中国痴呆患者中的作用：P301L家系研究和文献综述
DOI：
10.2147/ndt.s155521
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发表时间：
2018
影响因子：
3.2
通讯作者：
Zhang JW
中科院分区：
文献类型：
--
作者：
He S;Chen S;Xia MR;Sun ZK;Huang Y;Zhang JW
背景与目的额颞叶痴呆（Frontotemporal dementia，FTD）是第二常见的老年性痴呆，以行为改变和语言障碍为特征。FTD的诊断主要依赖于神经影像学，有时也依赖于基因筛查。然而，中国FTD患者的遗传组分仍基本未知。中国仅报告了少数具有已确定突变的FTD病例。本研究报告了一个中国人行为变异型FTD家系的详细临床和神经影像学特征。本文还对MAPT基因突变在中国人痴呆中的作用进行了综述。方法通过对家系中所有患者的详细询问，总结该病的主要临床特征。通过直接测序筛选出4个候选基因（MAPT、PSEN 1、PSEN 2和APP）。收集先证者和健康突变携带者的结构磁共振成像（MRI）、动脉自旋标记MRI脑血流功能成像（ASL-MRI）和氟脱氧葡萄糖正电子发射断层扫描（FDG-PET）脑代谢。结果通过对候选基因（MAPT、PSEN 1、PSEN 2和APP）的直接测序，在先证者和3名未患病的家系成员中发现MAPT基因P301 L突变。受累病例的表型在家系内是一致的。在这例经遗传学证实的行为变异FTD（bvFTD）患者中，ASL-MRI上的低灌注图与FDG-PET上的低代谢图非常相似。该bvFTD的临床特征与功能性神经影像学上的低灌注或低代谢模式一致。东亚地区P301 L的表型与西方国家相似。结论对于遗传性FTD患者，应结合ASL-MRI和基因鉴定进行确诊。为了防止被低估，需要进一步研究MAPT基因突变在中国FTD患者中的作用。
Background and purpose Frontotemporal dementia (FTD) is the second most common presenile dementia characterized by behavioral changes and language impairment. The diagnosis of FTD relies heavily on neuroimaging, and sometimes on genetic screening. However, the genetic components in Chinese FTD patients remain largely unknown. Only a few FTD cases with established mutations have been reported in China. This study reported the detailed clinical and neuroimaging features in a Chinese behavioral variant FTD family. The role of MAPT gene mutation in Chinese dementia patients was also reviewed. Methods By detailed inquiry of all affected individuals in the family, this study summarized the main clinical features of the disease. Four candidate genes (MAPT, PSEN1, PSEN2, and APP) were screened by direct sequencing. Structural magnetic resonance imaging (MRI), functional imaging of cerebral blood flow with arterial spin-labeled MRI (ASL-MRI), and cerebral metabolism with fluorodeoxyglucose positron emission tomography (FDG-PET) were collected in the proband and healthy mutation carriers. Results By direct sequencing of candidate genes (MAPT, PSEN1, PSEN2, and APP), this study identified the P301L mutation in the MAPT gene in the proband and three unaffected family members. The phenotype of the affected cases was consistent within the pedigree. In this genetically proven behavioral variant FTD (bvFTD) patient, the maps of hypoperfusion on ASL-MRI look fairly similar to the hypometabolism on FDG-PET. The clinical feature for this bvFTD was in line with the hypoperfusion or hypometabolism pattern on functional neuroimagings. The phenotype of P301L in east Asia seems similar to western countries. Conclusion For the inherited FTD patients, ASL-MRI and genetic identification were strongly recommended for the final diagnosis. In case of being underestimated, the role of MAPT gene mutation in Chinese FTD patients warrants further investigation.