Non-synonymous GIGYF2 variants in Parkinson's disease from two Asian populations.
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.
Tan
Eng-King
EK
Department of Neurology, Singapore General Hospital, Singapore, Singapore. gnrtek@sgh.com.sg
Lin
Chin-Hslen
CH
Tai
Chun-Hwei
CH
Tan
Louis C
LC
Chen
Meng-Ling
ML
Li
R
R
Lim
Hui-Qin
HQ
Pavanni
Ratnagopal
R
Yuen
Yih
Y
Prakash
K M
KM
Zhao
Yi
Y
Wu
Ruey-Meei
RM
D000328:Adult; D017668:Age of Onset; D000368:Aged; D001208:Asia; D002352:Carrier Proteins / Q000235:genetics* / Q000502:physiology*; D016022:Case-Control Studies; D015331:Cohort Studies; D005192:Family Health; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000208:ethnology / Q000235:genetics*; D011110:Polymorphism, Genetic; D044465:White People
D002352:Carrier Proteins; C478016:GIGYF2 protein, human