Suggestive linkage to chromosome 19 in a large Cuban family with late-onset Parkinson's disease

• Published in: Movement disorders Vol. 18; no. 11; pp. 1240 - 1249
• Main Authors: Bertoli-Avella, Aida M., Giroud-Benitez, Jose L., Bonifati, Vincenzo, Alvarez-Gonzalez, Eduardo, Heredero-Baute, Luis, Van Duijn, Cornelia M., Heutink, Peter
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.11.2003; Wiley
• Subjects: Age Factors; Aged; Antiparkinson Agents - therapeutic use; autosomal dominant; Biological and medical sciences; Brain - diagnostic imaging; Brain - pathology; chromosome 19p13.3-q12; Chromosomes, Human, Pair 19 - genetics; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Female; Follow-Up Studies; genetic linkage; Genetic Linkage - genetics; genome scan; Haplotypes - genetics; Humans; late-onset; Levodopa - therapeutic use; Magnetic Resonance Imaging; Male; Medical sciences; Middle Aged; Neurology; Parkinson Disease - diagnosis; Parkinson Disease - drug therapy; Parkinson Disease - genetics; Parkinson's disease; Pedigree; Polymerase Chain Reaction; Severity of Illness Index; Tomography, X-Ray Computed; Central America; Cuba; America; West Indies; Chromosome 19; Human; Nervous system diseases; Late; Pathophysiology; Family study; Parkinson disease; Cerebral disorder; Age of onset; Central nervous system disease; Genetic linkage; Genetics; Degenerative disease; Extrapyramidal syndrome
• ISSN: 0885-3185; 1531-8257
• DOI: 10.1002/mds.10534

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. © 2003 Movement Disorder Society