The role of MAPT gene in Chinese dementia patients: a P301L pedigree study and brief literature review

Abstract

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.

Keywords:

• frontotemporal dementia
• MAPT
• arterial spin labeling MRI
• FDG-PET

Supplementary materials

Polymerase chain reaction (PCR) protocol

PCR was performed on 10 μL of reaction mixture at 95°C for 5 min, followed by 35 cycles of 95°C for 30 s, an annealing step for 30 s, and 72°C for 30 s, with a final extension at 72°C for 10 min.

Figure S1 Sequencing of exon 10 of the MAPT gene showing a hemozygous c.1907C>T mutation (p.P301L).

Note: The arrow indicates the 143 site on DNA sequencing chromatogram.

Table S1 MAPT primers

Acknowledgments

This study was supported by the National Natural Science Fund (81671068). The authors would like to thank all the family members in this study.

Disclosure

The authors report no conflicts of interest in this work.