In affected members of 4 unrelated European Caucasian families with Parkinson disease-11 (PARK11; 607688), Lautier et al. (2008) identified a heterozygous 167A-G transition in exon 2 of the GIGYF2 gene, resulting in an asn56-to-ser (N56S) substitution in a highly conserved region. Disease onset ranged from age 41 to 73 years. There were 2 unaffected disease carriers, suggesting incomplete penetrance.
Nichols et al. (2009) identified a heterozygous N56S substitution in 1 of 96 probands with familial PD showing linkage to the PARK11 locus on chromosome 2q. The N56S substitution was also identified in another proband from an extended sample of 566 multiplex PD families. In 1 family, 2 sisters with PD with onset at ages 58 and 63, respectively, carried the heterozygous mutation. A deceased parent was reportedly affected. In the second family, 1 patient with PD carried the mutation, another patient who reportedly had PD but was not examined, also carried the mutation, whereas 2 additional family members with PD did not carry the mutation. Thus, in the second family, the N56S substitution did not segregate completely with the disorder. The N56S substitution was not identified in 1,447 controls. Nichols et al. (2009) raised doubts about the pathogenicity of mutations in the GIGYF2 gene as causative for PD.
Zimprich et al. (2009) identified the N56S variant in 1 of 669 PD patients and in 1 of 1,051 control individuals. The patient with PD had an affected sister, who did not carry the N56S variant. The authors concluded that the N56S variant does not play a major role in the pathogenesis of PD.
