Mutational screening and zebrafish functional analysis of GIGYF2 as a Parkinson-disease gene.
The Grb10-Interacting GYF Protein-2 (GIGYF2) gene has been proposed as the Parkinson-disease (PD) gene underlying the PARK11 locus. However, association of GIGYF2 with PD has been challenged and a functional validation of GIGYF2 mutations is lacking. In this frame, we performed a mutational screening of GIGYF2 in an Italian PD cohort. Exons containing known mutations were analyzed in 552 cases and 552 controls. Thereafter, a subset of 184 familial PD cases and controls were subjected to a full coding-exon screening. These analyses identified 8 missense variations in 9 individuals (4 cases, 5 controls). Furthermore, we developed a zebrafish model of gigyf2 deficiency. Abrogation of gigyf2 function in zebrafish embryos did not lead to a drastic cell loss in diencephalic dopaminergic (DA) neuron clusters, suggesting that gigyf2 is not required for DA neuron differentiation. Notably, gigyf2 functional abrogation did not increase diencephalic DA neurons susceptibility to the PD-inducing drug MPP+. These data, together with those recently reported by other groups, suggest that GIGYF2 is unlikely to be the PARK11 gene.
Guella
Ilaria
I
Dipartimento di Biologia e Genetica per le Scienze Mediche, Università degli Studi di Milano, Milan, Italy.
Pistocchi
Anna
A
Asselta
Rosanna
R
Rimoldi
Valeria
V
Ghilardi
Anna
A
Sironi
Francesca
F
Trotta
Luca
L
Primignani
Paola
P
Zini
Michela
M
Zecchinelli
Anna
A
Coviello
Domenico
D
Pezzoli
Gianni
G
Del Giacco
Luca
L
Duga
Stefano
S
Goldwurm
Stefano
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D019976:Cloning, Organism; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000235:genetics*; D015027:Zebrafish
D002352:Carrier Proteins; C478016:GIGYF2 protein, human