title: Large French-Canadian family with Lewy body parkinsonism: exclusion of known loci.
abstract: The identification of rare, large families with Parkinson's disease (PD) has provided important clues that have contributed to our understanding of this complex disorder. We have identified a large French-Canadian kindred that spans five generations consisting of more than 90 individuals. A total of 65 individuals now have been examined, had venous blood drawn, and DNA extracted. Two-point and multipoint linkage analysis was performed to assess linkage to known PD genes or loci. Within the third and fourth generations of this family there are 10 living, plus 3 deceased members with well-documented levodopa responsive parkinsonism. Autopsy results on 1 member demonstrated the loss of pigmented neurons in the substantia nigra and the presence of alpha-synuclein positive Lewy bodies. Four of the PD patients have prominent postural and kinetic tremors that preceded their parkinsonism by up to 10 years. Two other individuals within the family have prominent isolated postural and kinetic tremors without parkinsonism. The alpha-synuclein(4q21.3-23), Parkin(6q25.2-27), PARK3 (2p13), PARK4, and ubiquitin carboxy terminal hydrolase-L1 (4p14-16.3) and PARK6 and PARK7 (1p35-36) loci were excluded in this kindred using closely linked markers. The clinical and pathological features of this family are consistent with the diagnosis of PD. This family further demonstrates the known genetic heterogeneity in PD and is large enough that a genome-wide screen has been undertaken in an effort to identify a novel PD gene.
authors.affiliation: Ottawa Health Research Institute, Ottawa, Canada. dagrimes@ottawahospital.on.ca
authors.forename: David A
authors.initials: DA
authors.lastname: Grimes
authors.forename: J David
authors.initials: JD
authors.lastname: Grimes
authors.forename: Lem
authors.initials: L
authors.lastname: Racacho
authors.forename: Kylie A
authors.initials: KA
authors.lastname: Scoggan
authors.forename: Fabin
authors.initials: F
authors.lastname: Han
authors.forename: Betty Anne
authors.initials: BA
authors.lastname: Schwarz
authors.forename: John
authors.initials: J
authors.lastname: Woulfe
authors.forename: Dennise
authors.initials: D
authors.lastname: Bulman
mesh_terms: D000328:Adult; D000368:Aged; D000978:Antiparkinson Agents / Q000627:therapeutic use; D001921:Brain / Q000473:pathology; D002869:Chromosome Aberrations; D002874:Chromosome Mapping; D005260:Female; D005500:Follow-Up Studies; D005799:Genes, Dominant; D005819:Genetic Markers / Q000235:genetics*; D005820:Genetic Testing; D006801:Humans; D016631:Lewy Bodies / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009864:Ontario; D020734:Parkinsonian Disorders / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D010375:Pedigree
chemical_list: D000978:Antiparkinson Agents; D005819:Genetic Markers