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while those with mutations in the MAPT gene tend the population-specific variants. Second, most of
to possess both α-synuclein and tau pathologies. In the current genetic studies are focused on sequence
contrast, except for nonspecific neuronal loss and variations (i.e. point mutations or SNPs) and much less
gliosis, no histopathological hallmark was revealed have been directed to copy-number variations (CNVs),
in most of the AR-JP patients caused by mutations whose pathogenic or predisposing effects sometimes
in the parkin gene. [146] Moreover, many variations in are even more evident and important. Dosage mutations
these genes are not only associated with increased of the parkin gene, for instance, have been suggested
risk for PD, but strongly correlate with certain profiles to be more pathogenic than the sequence mutations for
of the disease. Hence, it is reasonable to assume that familial PD among Europeans. Therefore, large-scale
genetically determined loci, especially when combined and multi-central analysis of CNVs are urgently needed
with pathological and clinical information, can help to improve the image of risk genetic variants for PD.
in establishing a classification for PD. In a recent Third, the work on genetic mechanisms underlying
study, we have investigated clinical profiles of PD PD is far away from just identifying mutations or risk
related to LRRK2 (LRRK2-PD), GBA (GBA-PD) variant, variants. We have to figure out how these variants
or none of the variants (idiopathic PD, IPD). [148] As act on the disease, e.g. how they interact with other
a result, LRRK2-PD is largely similar to IPD, while genes and/or environmental factors, and how they are
GBA-PD patients had an earlier onset and more linked to pathophysiological pathways involved in PD.
frequent and severe nonmotor symptoms. These results In addition, prospective studies of presymptomatic
favor the feasibility of genetic classification of PD. carriers of mutations or risk genetic variants of PD
However, since much of our knowledge about the genes are necessary to confirm their genetic roles in
genetic-pathologic-clinical axis of parkinsonism is the disease development and progression.
quite limited so far, there is still a long way ahead before
a rational nosology for parkinsonian disorders linked ACKNOWLEDGMENTS
to their genetic underpinnings is made and before the
classification becomes a practice guideline. This study was supported by grants from National Natural
Science Foundation of China (No. 81371320), the Project for
CONCLUDING REMARKS AND FUTURE Young and Middle-Aged Talents of Fujian Health Care System,
RESEARCH CONCERNS No. 2013-ZQN-JC-29 to Dr. Chao-Dong Wang, and the Ministry
of Science and Technology of China (2012AA02A514),
The past decade has been an exciting time for the National Basic Research Development Program of
investigators involved in genetic research in PD. The China (2011CB504101) to Dr. Piu Chan.
rapidly emerging evidences of the genetic contribution
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