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Monogenic Parkinson's disease and parkinsonism: clinical phenotypes and frequencies of known mutations.
Parkinsonism Relat Disord. 2013 Apr; 19(4):407-15.PR

Abstract

Mutations in seven genes are robustly associated with autosomal dominant (SNCA, LRRK2, EIF4G1, VPS35) or recessive (parkin/PARK2, PINK1, DJ1/PARK7) Parkinson's disease (PD) or parkinsonism. Changes in a long list of additional genes have been suggested as causes for parkinsonism or PD, including genes for hereditary ataxias (ATXN2, ATXN3, FMR1), frontotemporal dementia (C9ORF72, GRN, MAPT, TARDBP), DYT5 (GCH1, TH, SPR), and others (ATP13A2, CSF1R, DNAJC6, FBXO, GIGYF2, HTRA2, PLA2G6, POLG, SPG11, UCHL1). This review summarizes the clinical features of diseases caused by mutations in these genes, and their frequencies. Point mutations and multiplications in SNCA cause cognitive or psychiatric symptoms, parkinsonism, dysautonomia and myoclonus with widespread alpha-synuclein pathology in the central and peripheral nervous system. LRRK2 mutations may lead to a clinical phenotype closely resembling idiopathic PD with a puzzling variety in neuropathology. Mutations in parkin/PARK2, PINK1 or DJ1/PARK7 may cause early-onset parkinsonism with a low risk for cognitive decline and a pathological process usually restricted to the brainstem. Carriers of mutations in the other genes may develop parkinsonism with or without additional symptoms, but rarely a disease resembling PD. The pathogenicity of several mutations remains unconfirmed. Although some mutations occur with high frequency in specific populations, worldwide all are very rare. The genetic cause of the majority of patients with sporadic or hereditary PD remains unknown in most populations. Clinical genetic testing is useful for selected patients. Testing strategies need to be adapted individually based on clinical phenotype and estimated frequency of the mutation in the patient's population.

Authors+Show Affiliations

Dept. for Neurology, Lund University and Skåne University Hospital, Getingevägen 4, 22185 Lund, Sweden. andreas.puschmann@med.lu.se

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

23462481

Citation

Puschmann, Andreas. "Monogenic Parkinson's Disease and Parkinsonism: Clinical Phenotypes and Frequencies of Known Mutations." Parkinsonism & Related Disorders, vol. 19, no. 4, 2013, pp. 407-15.
Puschmann A. Monogenic Parkinson's disease and parkinsonism: clinical phenotypes and frequencies of known mutations. Parkinsonism Relat Disord. 2013;19(4):407-15.
Puschmann, A. (2013). Monogenic Parkinson's disease and parkinsonism: clinical phenotypes and frequencies of known mutations. Parkinsonism & Related Disorders, 19(4), 407-15. https://doi.org/10.1016/j.parkreldis.2013.01.020
Puschmann A. Monogenic Parkinson's Disease and Parkinsonism: Clinical Phenotypes and Frequencies of Known Mutations. Parkinsonism Relat Disord. 2013;19(4):407-15. PubMed PMID: 23462481.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Monogenic Parkinson's disease and parkinsonism: clinical phenotypes and frequencies of known mutations. A1 - Puschmann,Andreas, Y1 - 2013/02/23/ PY - 2012/06/14/received PY - 2013/01/20/revised PY - 2013/01/28/accepted PY - 2013/3/7/entrez PY - 2013/3/7/pubmed PY - 2013/9/7/medline SP - 407 EP - 15 JF - Parkinsonism & related disorders JO - Parkinsonism Relat Disord VL - 19 IS - 4 N2 - Mutations in seven genes are robustly associated with autosomal dominant (SNCA, LRRK2, EIF4G1, VPS35) or recessive (parkin/PARK2, PINK1, DJ1/PARK7) Parkinson's disease (PD) or parkinsonism. Changes in a long list of additional genes have been suggested as causes for parkinsonism or PD, including genes for hereditary ataxias (ATXN2, ATXN3, FMR1), frontotemporal dementia (C9ORF72, GRN, MAPT, TARDBP), DYT5 (GCH1, TH, SPR), and others (ATP13A2, CSF1R, DNAJC6, FBXO, GIGYF2, HTRA2, PLA2G6, POLG, SPG11, UCHL1). This review summarizes the clinical features of diseases caused by mutations in these genes, and their frequencies. Point mutations and multiplications in SNCA cause cognitive or psychiatric symptoms, parkinsonism, dysautonomia and myoclonus with widespread alpha-synuclein pathology in the central and peripheral nervous system. LRRK2 mutations may lead to a clinical phenotype closely resembling idiopathic PD with a puzzling variety in neuropathology. Mutations in parkin/PARK2, PINK1 or DJ1/PARK7 may cause early-onset parkinsonism with a low risk for cognitive decline and a pathological process usually restricted to the brainstem. Carriers of mutations in the other genes may develop parkinsonism with or without additional symptoms, but rarely a disease resembling PD. The pathogenicity of several mutations remains unconfirmed. Although some mutations occur with high frequency in specific populations, worldwide all are very rare. The genetic cause of the majority of patients with sporadic or hereditary PD remains unknown in most populations. Clinical genetic testing is useful for selected patients. Testing strategies need to be adapted individually based on clinical phenotype and estimated frequency of the mutation in the patient's population. SN - 1873-5126 UR - https://www.unboundmedicine.com/medline/citation/23462481/Monogenic_Parkinson's_disease_and_parkinsonism:_clinical_phenotypes_and_frequencies_of_known_mutations_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1353-8020(13)00055-2 DB - PRIME DP - Unbound Medicine ER -