Non-synonymous GIGYF2 variants in Parkinson's disease from two Asian populations
Journal
Human Genetics
Journal Volume
126
Journal Issue
3
Pages
425-430
Date Issued
2009
Author(s)
Tan E.-K.
Lin C.-H.
Tan L.C.
Chen M.-L.
Li R.
Lim H.-Q.
Pavanni R.
Yuen Y.
Prakash K.M.
Zhao Y.
Abstract
Mutations in the GIGYF2 gene at the PARK11 locus have recently been reported in Parkinson's disease (PD). However, the pathogenicity of some of these mutations has been debated. We conducted a comprehensive genetic analysis of the entire GIGYF2 gene in a cohort of young onset and familial PD patients, followed up with screening of specific variants in a separate group of PD and healthy controls. A total of 850 study subjects [450 Parkinson's disease (PD) patients and 400 controls] from two Asian countries were included. Our analysis revealed 17 variants distributed across the entire GIGYF2 gene. Ten of these were novel variants out of which eight were non-synonymous (all heterozygous). Out of these eight, half were novel polymorphic variants (0.2-2%) whereas four were novel non-synonymous variants which were not detected in healthy controls. The seven PD patients with non-synonymous variants had a mean age and age at onset of 55.3 and 50.9 years. All had typical features of PD and only one had a positive family history. The collective frequency of these non-synonymous variants was higher in PD compared to controls (1.6 vs. 0%, P = 0.016, relative risk 1.9, 95% CI 1.2, 1.9). None of the previously reported pathogenic mutations in Italian and French patients were present in our cohort. Our data suggest that GIGYF2 is unlikely to play a major role in our Asian populations. Rare non-synonymous variants appeared to be enriched in our PD patients compared to healthy controls. However, in vivo functional studies and segregation analysis in large pedigrees will be needed to determine if these single heterozygous variants represent rare mutations, risk alleles or benign polymorphisms. ? Springer-Verlag 2009.
SDGs
Other Subjects
gene product; glucosylceramidase; levodopa; protein GIGYF2; unclassified drug; adult; aged; article; Asian; attributable risk; bradykinesia; clinical feature; controlled study; dementia; exon; family history; female; gene deletion; gene frequency; gene insertion; gene locus; gene mutation; genetic screening; genetic variability; human; in vivo study; major clinical study; male; missense mutation; nucleotide sequence; Parkinson disease; pedigree; population genetics; priority journal; rigidity; sequence alignment; Singapore; Taiwan; tremor; Adult; Age of Onset; Aged; Asia; Carrier Proteins; Case-Control Studies; Cohort Studies; European Continental Ancestry Group; Family Health; Female; Genetic Variation; Humans; Male; Middle Aged; Parkinson Disease; Polymorphism, Genetic
Type
journal article