Genetics of frontotemporal dementia in China

Abstract

Backgbround: Frontotemporal dementia (FTD) is the second most common presenile dementia, characterized by prominent behavioral, language, and cognitive impairment, which has a strong genetic component contributing to its pathogenesis. Due to geographical and ethnic variability, the prevalence of the causative genes of FTD may be different. Methods: To explore the genetics of FTD in the Chinese population, we reviewed 97 closely related studies that were searched in PubMed and Web of Science. In this review, we summarized the characteristics of each FTD gene. We also reassessed their pathogenicity and revised some mutations from pathogenic to uncertain significance according to the American College of Medical Genetics and Genomics (ACMG). Results: Thirty-two rare variants in genes of MAPT, GRN, C9orf72, CHCHD10, VCP, and TBK1 were identified in Chinese FTD populations, including 25 pathogenic mutations and seven variants of uncertain significance (VUS). Among them, the frequency of rare variants in the CHCHD10 gene was the highest. Surprisingly, twelve variants reported as pathogenic mutations were revised as VUS by ACMG. The correlations between genes and clinical manifestations were MAPT and frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), GRN and frontotemporal lobar degeneration with TDP-43 proteinopathy (FTLD-TDP), C9orf72/CHCHD10/TBK1 and amyotrophic lateral sclerosis (ALS)-FTD spectrum, and VCP corresponds inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia (IBMPFD). Conclusions: It is necessary to strictly interpret the contributions of genes to diseases by ACMG. MAPT is the most common pathogenic gene for FTD in China.

Keywords:

• Frontotemporal dementia
• amyotrophic lateral sclerosis
• genetics
• China

Acknowledgments

The authors are grateful to all subjects who participated in this study.

Declaration of interest

The authors declare no competing interests.

Table 1 The correlation between genes and clinical manifestations in Chinese FTD patients.

Additional information

Funding

This study was financially supported by the National Natural Science Foundation of China [81671075 and 81971029 to Lu Shen; 81701134 to Bin Jiao; 81901171 to Xinxin Liao], the National Key R&D Program of China [2017YFC0840100 and 2017YFC0840104 to Lu Shen; 2018YFC1312003 to Junling Wang], the Provincial Technology Innovation Guidance Plan Project of Hunan [2018SK52601 to Bin Jiao], and the Youth Science Foundation of Xiangya Hospital [2018Q020 to Xinxin Liao].