Monogenic Parkinson’s Disease: Genotype, Phenotype, Pathophysiology, and Genetic Testing
1
Department of Neurology, Concord Repatriation General Hospital, Concord, NSW 2139, Australia
2
Sydney Medical School, University of Sydney, Camperdown, NSW 2050, Australia
3
Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia
4
Raphael Recanati Genetics Institute, Rabin Medical Center, Beilinson Hospital, Petah Tikva 4941492, Israel
5
Department of Neurology, Rabin Medical Center, Beilinson Hospital, Petah Tikva 4941492, Israel
6
Molecular Medicine Laboratory, Concord Repatriation General Hospital, Concord, NSW 2139, Australia
*
Author to whom correspondence should be addressed.
Academic Editors: Suzanne Lesage and Joanne Trinh
Genes 2022, 13(3), 471; https://doi.org/10.3390/genes13030471
Received: 4 February 2022
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Revised: 24 February 2022
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Accepted: 2 March 2022
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Published: 7 March 2022
(This article belongs to the Special Issue Parkinson's Disease: Genetics and Pathogenesis)
Parkinson’s disease may be caused by a single pathogenic variant (monogenic) in 5–10% of cases, but investigation of these disorders provides valuable pathophysiological insights. In this review, we discuss each genetic form with a focus on genotype, phenotype, pathophysiology, and the geographic and ethnic distribution. Well-established Parkinson’s disease genes include autosomal dominant forms (SNCA, LRRK2, and VPS35) and autosomal recessive forms (PRKN, PINK1 and DJ1). Furthermore, mutations in the GBA gene are a key risk factor for Parkinson’s disease, and there have been major developments for X-linked dystonia parkinsonism. Moreover, atypical or complex parkinsonism may be due to mutations in genes such as ATP13A2, DCTN1, DNAJC6, FBXO7, PLA2G6, and SYNJ1. Furthermore, numerous genes have recently been implicated in Parkinson’s disease, such as CHCHD2, LRP10, TMEM230, UQCRC1, and VPS13C. Additionally, we discuss the role of heterozygous mutations in autosomal recessive genes, the effect of having mutations in two Parkinson’s disease genes, the outcome of deep brain stimulation, and the role of genetic testing. We highlight that monogenic Parkinson’s disease is influenced by ethnicity and geographical differences, reinforcing the need for global efforts to pool large numbers of patients and identify novel candidate genes.
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MDPI and ACS Style
Jia, F.; Fellner, A.; Kumar, K.R. Monogenic Parkinson’s Disease: Genotype, Phenotype, Pathophysiology, and Genetic Testing. Genes 2022, 13, 471. https://doi.org/10.3390/genes13030471
AMA Style
Jia F, Fellner A, Kumar KR. Monogenic Parkinson’s Disease: Genotype, Phenotype, Pathophysiology, and Genetic Testing. Genes. 2022; 13(3):471. https://doi.org/10.3390/genes13030471
Chicago/Turabian StyleJia, Fangzhi, Avi Fellner, and Kishore Raj Kumar. 2022. "Monogenic Parkinson’s Disease: Genotype, Phenotype, Pathophysiology, and Genetic Testing" Genes 13, no. 3: 471. https://doi.org/10.3390/genes13030471
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