In affected members of 12 unrelated Italian or French families with PD, Lautier et al. (2008) identified 7 different heterozygous mutations in the GIGYF2 gene (see, e.g., 612003.0001-612003.0004). Inheritance was autosomal dominant with evidence of incomplete penetrance. Clinical ... In affected members of 12 unrelated Italian or French families with PD, Lautier et al. (2008) identified 7 different heterozygous mutations in the GIGYF2 gene (see, e.g., 612003.0001-612003.0004). Inheritance was autosomal dominant with evidence of incomplete penetrance. Clinical features were similar to that of idiopathic PD. Bras et al. (2009) sequenced the entire coding region of GIGYF2 in a series of 267 Portuguese and 460 North American PD samples. The authors found 3 previously published mutations, including N457T (612003.0002), among neurologically normal control individuals. The authors suggested that mutations in GIGYF2 are not strongly related to the development of the disease in either of these populations. Nichols et al. (2009) did not identify 5 of the 7 GIGYF2 variants reported by Lautier et al. (2008) among 96 probands with PD linked to chromosome 2q or in an extended sample of 566 multiplex PD families. One variant (N56S; 612003.0001) was found in 2 families and showed incomplete penetrance. Another variant (N457T; 612003.0002) was demonstrated not to segregate with the disorder in 1 family, raising doubts about its pathogenicity. Nichols et al. (2009) concluded that there was no consistent evidence that variation in the GIGYF2 gene contributes significantly to PD, and suggested that variation in another gene at this locus accounts for the disorder. 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. In addition, the N457T variant was found in 1 patient of Egyptian origin and in 3 controls of European origin, but not in 50 Egyptian controls. The authors concluded that neither variant plays a major role in the pathogenesis of PD. Tan et al. (2009) identified 4 different heterozygous mutations in the GIGYF2 gene (see, e.g., K421R; 612003.0005) in 7 (1.6%) of 450 patients with Parkinson disease from Taiwan and Singapore. The mutations were not identified in 400 controls. One patient had a positive family history, but the family was too small for segregation analysis. All patients had typical features of PD, with a mean age of onset ranging from 39 to 67 years. None of the mutations reported by Lautier et al. (2008) were found. Tan et al. (2009) emphasized that their results should be interpreted with caution, and that replication studies should be performed to establish conclusively if the variants are indeed pathogenic.