Cited by 788Parkinson's Disease Mechanisms and TreatmentsGenetic Associations and EpidemiologyDeep Brain Stimulation and Movement Disorders

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Mapping of a Gene for Parkinson's Disease to Chromosome 4q21-q23

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Polymeropoulos, Mihael H., Higgins, Joseph J., Golbe, Lawrence I., Johnson, William G., Ide, Susan E., Di Iorio, Giuseppe, Sanges, Giuseppe, Stenroos, Edward S., Pho, Lana T., Schaffer, Alejandro A., Lazzarini, Alice M., Nussbaum, Robert L., Duvoisin, Roger C.·1996·Science

DOI 10.1126/science.274.5290.1197

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Abstract

Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease, affecting approximately 1 percent of the population over age 50. Recent studies have confirmed significant familial aggregation of PD and a large number of large multicase families have been documented. Genetic markers on chromosome 4q21-q23 were found to be linked to the PD phenotype in a large kindred with autosomal dominant PD, with a Zmax = 6.00 for marker D4S2380. This finding will facilitate identification of the gene and research on the pathogenesis of PD.

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Background
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Background
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Background
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Background
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Background
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“Pathogenic characters of typical PD comprise loss of dopaminergic neurons in the substantia nigra (SN) and the manifestation of Lewy bodies, intracellular cytoplasmic inclusions, in enduring neurons in various areas of the brain, mainly the SN [2].”
Background
The genetics of Parkinson's disease and parkinsonian syndromes
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Clinical Overview and Phenomenology of Movement Disorders
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“It is well known that A53T and E46 K mutations increases aggregation propensity of αS (Choi et al., 2004; Polymeropoulos et al., 1996), and hence H50Q and G51D mutation present in the N-terminal region of αS is expected to have similar effect.”
Background
“Janus-Faced” α-Synuclein: Role in Parkinson’s Disease
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“The link between mutant α-syn and PD was established in an autosomal dominant form of PD with the missense mutation in the chromosome 4q21q23 (Polymeropoulos et al., 1996).”
Background
Parkinson's disease is not a long‐latency illness
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“The first gene to be unequivocally related to PD was the α-synuclein gene (SNCA) [64].”
Background
Common genetic risk for Parkinson's disease and dysfunction of the endo-lysosomal system
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“…coding change at codon 53, A53T) in the SNCA gene causative for an autosomal dominant form of PD in 1997, which ushered in a new era of human molecular genetics for PD. SNCA encodes α -synu- clein, the major constituent of Lewy bodies, and a central player in the aetiology of PD (box 1) [15 – 20].”
Background
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Festination Correlates with SNCA Polymorphism in Chinese Patients with Parkinson’s Disease
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Authors: Polymeropoulos, M. H., Higgins, J. J., Golbe, L. I., Johnson, W. G., Ide, S. E., Di Iorio, G., Sanges, G., Stenroos, E. S., Pho, L. T., Schaffer, A. A., Lazzarini, A. M., Nussbaum, R. L., & Duvoisin, R. C.
Affiliations: National Institutes of Health (US)
University of Medicine and Dentistry of New Jersey (US)
G. Di Iorio and G. Sanges, Istituto di Scienze Neurologiche, Facoltá di Medicina, Seconda Universitá degli Studi di Napoli, Naples, Italy.
University of Campania "Luigi Vanvitelli" (IT)
M. H. Polymeropoulos, S. E. Ide, A. A. Schaffer, R. L. Nussbaum, Laboratory of Genetic Disease Research, National Center for Human Genome Research, National Institutes of Health, Bethesda, MD 20892-1430, USA.
ORCID: Polymeropoulos, Mihael H.
Higgins, Joseph J.
Golbe, Lawrence I.
Nussbaum, Robert L.
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 1996-11-15
Volume: 274
Issue: 5290
Pages: 1197-1199
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.274.5290.1197
OpenAlex: W1999893655
Cited by: 788
References: 27
Citations by year: 2026: 9 · 2025: 29 · 2024: 21 · 2023: 27 · 2022: 26 · 2021: 18 · 2020: 41 · 2019: 20 · 2018: 21 · 2017: 26 · 2016: 18 · 2015: 23 · 2014: 27 · 2013: 23 · 2012: 17
FWCI: 38.08
Type: journal article
Language: en
Open access: green
zenodo.org
Licence: public-domain
Locations: Science (publishedVersion)
PubMed (publishedVersion)
Zenodo (CERN European Organization for Nuclear Research) (submittedVersion, public-domain)
Topics: Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Health Sciences › Medicine › Clinical Neurology › Deep Brain Stimulation and Movement Disorders
Keywords: Parkinson's disease, genetic linkage, autosomal dominant inheritance, familial aggregation, gene mapping, neurodegenerative diseases
MeSH terms: Chromosome Mapping, Chromosomes, Human, Pair 4, Female, Genetic Markers, Humans, Genetic Linkage, Lod Score, Male, Parkinson Disease, Pedigree, Phenotype

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Mapping of a Gene for Parkinson's Disease to Chromosome 4q21-q23

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