Variation in GIGYF2 is not associated with Parkinson disease.
OBJECTIVE
A recent study reported that mutations in a gene on chromosome 2q36-37, GIGYF2, result in Parkinson disease (PD). We have previously reported linkage to this chromosomal region in a sample of multiplex PD families, with the strongest evidence of linkage obtained using the subset of the sample having the strongest family history of disease and meeting the strictest diagnostic criteria. We have tested whether mutations in GIGYF2 may account for the previously observed linkage finding.


METHODS
We sequenced the GIGYF2 coding region in 96 unrelated patients with PD used in our original study that contributed to the chromosome 2q36-37 linkage signal. Subsequently, we genotyped the entire sample of 566 multiplex PD kindreds as well as 1,447 controls to test whether variants in GIGYF2 are causative or increase susceptibility for PD.


RESULTS
We detected three novel variants as well as one of the previously reported seven variants in a total of five multiple PD families; however, there was no consistent evidence that these variants segregated with PD in these families. We also did not find a significant increase in risk for PD among those inheriting variants in GIGYF2 (p = 0.28).


CONCLUSIONS
We believe that variation in a gene other than GIGYF2 accounts for the previously reported linkage finding on chromosome 2q36-37.
Nichols
W C
WC
Division of Human Genetics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA. bill.nichols@cchmc.org
Kissell
D K
DK
Pankratz
N
N
Pauciulo
M W
MW
Elsaesser
V E
VE
Clark
K A
KA
Halter
C A
CA
Rudolph
A
A
Wojcieszek
J
J
Pfeiffer
R F
RF
Foroud
T
T
D000368:Aged; D001483:Base Sequence / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics*; D002874:Chromosome Mapping / Q000379:methods; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D008040:Genetic Linkage / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D016366:Open Reading Frames / Q000235:genetics; D010300:Parkinson Disease / Q000235:genetics*; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
D002352:Carrier Proteins; C478016:GIGYF2 protein, human