PARK11 is not linked with Parkinson's disease in European families

Abstract

Parkinson's disease (PD) is a genetically heterogeneous disease. Recently, significant linkage has been reported to a 39.5 cM region on the long arm of chromosome 2 (2q36-37; PARK11) in North American Parkinson families under an autosomal dominant model of inheritance. We have performed a replication study to confirm linkage to this region in a European population. Linkage analysis in 153 individuals from 45 European families with a strong family history of PD did not show any significant LOD score in this region. Therefore, PARK11 does not seem to play a major role for familial PD in the European population.

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

“…A genome-wide association study also confirmed the locus [252], but it was not confirmed in a European linkage study [253]. In 2008, 7 different heterozygous mutations were identified in the GIGYF2 gene (located at the linkage peak) in French and Italian PD cases with family history of PD [172].…”

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.…”

Genetics of Parkinsonism

“…The gene on chromosome 2q36-q37 remains to be identified. Indeed, these results were not replicated recently in a European population [52].…”