Suggestive linkage to chromosome 19 in a large Cuban family with late-onset Parkinson's disease.
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.
Bertoli-Avella
Aida M
AM
Department of Epidemiology and Biostatistics, Erasmus Medical Center, Rotterdam, The Netherlands. a.bertoliavella@erasmusmc.nl
Giroud-Benitez
Jose L
JL
Bonifati
Vincenzo
V
Alvarez-Gonzalez
Eduardo
E
Heredero-Baute
Luis
L
van Duijn
Cornelia M
CM
Heutink
Peter
P
D000367:Age Factors; D000368:Aged; D000978:Antiparkinson Agents / Q000627:therapeutic use; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D008040:Genetic Linkage / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D010375:Pedigree; D016133:Polymerase Chain Reaction; D012720:Severity of Illness Index; D014057:Tomography, X-Ray Computed
D000978:Antiparkinson Agents; D007980:Levodopa