title: Evaluation of the role of Nurr1 in a large sample of familial Parkinson's disease.
abstract: Parkinson's disease (PD) is a common neurodegenerative disorder in humans with wide variability in the age of disease onset. Although the disease has been thought previously to occur sporadically in most patients, there is increasing evidence of a genetic contribution to the disorder. Recently, a polymorphic variant within intron 6 of the Nurr1 gene was reported to be associated with sporadic and familial PD. In an effort to identify susceptibility genes for PD, we have collected 783 PD patients from 372 families and 397 healthy controls from 217 families. PD patients and healthy controls were genotyped for the intron 6 insertion polymorphism by BseRI restriction endonuclease digestion. No significant difference in either homozygosity or heterozygosity for the 7048G7049 (IVS6 1361 +16insG) polymorphism was detected in the PD patient cohort as compared with the panel of healthy controls. Moreover, direct sequencing of exon 1 of the Nurr1 gene in PD patients failed to detect either of the two recently reported Nurr1 mutations identified in a small subset of a PD patient cohort. Taken together, these data suggest that genetic alteration at the Nurr1 locus is not a significant risk factor for the development of Parkinson's disease in our large sample of familial PD patients.
authors.affiliation: Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA. bill.nichols@cchmc.org
authors.forename: William C
authors.initials: WC
authors.lastname: Nichols
authors.forename: Sean K
authors.initials: SK
authors.lastname: Uniacke
authors.forename: Nathan
authors.initials: N
authors.lastname: Pankratz
authors.forename: Terry
authors.initials: T
authors.lastname: Reed
authors.forename: David K
authors.initials: DK
authors.lastname: Simon
authors.forename: Cheryl
authors.initials: C
authors.lastname: Halter
authors.forename: Alice
authors.initials: A
authors.lastname: Rudolph
authors.forename: Clifford W
authors.initials: CW
authors.lastname: Shults
authors.forename: P Michael
authors.initials: PM
authors.lastname: Conneally
authors.forename: Tatiana
authors.initials: T
authors.lastname: Foroud
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004251:DNA Transposable Elements / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007438:Introns / Q000235:genetics; D008875:Middle Aged; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D010300:Parkinson Disease / Q000235:genetics*; D017354:Point Mutation / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D004251:DNA Transposable Elements; D004268:DNA-Binding Proteins; C539882:NR4A2 protein, human; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D014157:Transcription Factors