GIGYF2 mutations are not a frequent cause of familial Parkinson's disease

Drosophila Gyf/GRB10 interacting GYF protein is an autophagy regulator that controls neuron and muscle homeostasis

“…14 Although GIGYF2/PARK11 mutations are actually excluded from the frequent causes of PD in the general human population, [57][58][59][60] GIGYF2 may still play important roles in maintaining neuronal homeostasis and preventing neurodegeneration. Gigyf2 ¡/¡ mice are reported to exhibit perinatal mortality and Gigyf2 C/¡ mice display early onset of age-associated neurodegenerative phenotypes that include neuronal protein inclusion and a significant decline in mobility.…”

Epidemiology and etiology of Parkinson’s disease: a review of the evidence

“…A Belgian study found two heterozygous mutations in three sporadic PD cases (out of altogether 305 sporadic and familial cases), but the pathogenicity of these mutations was not clear [255]. Another study of North American and Portuguese PD cases found two of these mutations, but only in healthy persons [256], and a study of primarily Italian cases found no mutations [257], casting doubt whether the GIGYF2 is a causative PD gene. In a large sample of US and Norwegian PD cases (in total 1,139 cases), one of the originally reported [172] mutations was identified in three US sporadic cases, but none of the other mutations were found [258].…”

Summary of GIGYF2 studies in Parkinson’s disease: the burden of proof

“…However, in recent months, at least 10 replication studies [6–15] including the latest one by Samaranch et al. [15] in this journal have provided conflicting data to cast considerable doubt on the causal role of GIGYF2 .…”

“…[8] and Di Fonzo et al. [9] sequenced the gene in Italian familial PD cases (combined sample size larger than that of Lautier et al. ) but found no mutations.…”