title: Mutational screening and zebrafish functional analysis of GIGYF2 as a Parkinson-disease gene.
abstract: 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.
authors.affiliation: Dipartimento di Biologia e Genetica per le Scienze Mediche, Università degli Studi di Milano, Milan, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Guella
authors.forename: Anna
authors.initials: A
authors.lastname: Pistocchi
authors.forename: Rosanna
authors.initials: R
authors.lastname: Asselta
authors.forename: Valeria
authors.initials: V
authors.lastname: Rimoldi
authors.forename: Anna
authors.initials: A
authors.lastname: Ghilardi
authors.forename: Francesca
authors.initials: F
authors.lastname: Sironi
authors.forename: Luca
authors.initials: L
authors.lastname: Trotta
authors.forename: Paola
authors.initials: P
authors.lastname: Primignani
authors.forename: Michela
authors.initials: M
authors.lastname: Zini
authors.forename: Anna
authors.initials: A
authors.lastname: Zecchinelli
authors.forename: Domenico
authors.initials: D
authors.lastname: Coviello
authors.forename: Gianni
authors.initials: G
authors.lastname: Pezzoli
authors.forename: Luca
authors.initials: L
authors.lastname: Del Giacco
authors.forename: Stefano
authors.initials: S
authors.lastname: Duga
authors.forename: Stefano
authors.initials: S
authors.lastname: Goldwurm
mesh_terms: 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
chemical_list: D002352:Carrier Proteins; C478016:GIGYF2 protein, human