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The identification of disease genes using family-based approaches has provided important insights into the pathogenesis of Parkinson's disease (PD) demonstrating the importance of genetic studies on monogenic forms of the disease. We studied a large Cuban family with typical, late-onset PD and probable autosomal dominant inheritance. Mean age at onset was 61.2 years (+/- 12.53, 45-76). Other phenotypes such as essential tremor and atypical parkinsonism were observed in this family. We carried out a genome-wide scan and linkage analyses. The genetic data were analyzed using a conservative model in which only patients with clinically definite or likely PD were considered affected, other phenotypes were regarded as "unknown." Multipoint analyses yielded a maximum LOD of 2.26 between markers D19S221 and D19S840. Haplotype analysis showed a region on chromosome 19 shared by six of seven PD patients. The essential tremor phenotype and the atypical parkinsonism do not segregate with this haplotype, suggesting a different etiology. Our findings suggest the presence of a novel locus for PD on chromosome 19p13.3-q12. We propose that an oligogenic model with moderate contribution of two or three genes rather than a "pure" monogenic model might explain better the wide range in age at onset, the reduced penetrance and the phenotypical variability observed in PD families.

Original publication

DOI

10.1002/mds.10534

Type

Journal article

Journal

Mov Disord

Publication Date

11/2003

Volume

18

Pages

1240 - 1249

Keywords

Age Factors, Aged, Antiparkinson Agents, Brain, Chromosomes, Human, Pair 19, Female, Follow-Up Studies, Genetic Linkage, Haplotypes, Humans, Levodopa, Magnetic Resonance Imaging, Male, Middle Aged, Parkinson Disease, Pedigree, Polymerase Chain Reaction, Severity of Illness Index, Tomography, X-Ray Computed