Mutation analysis of PINK1 gene in patients with early-onset Parkinsonism

Objective To determine the frequency of mutations in PINK1 in Chinese Han people with sporadic early-onset Parkinsonism (EOP). Methods DNA sequencing was used to detect point mutations and small deletions/insertions, and quantitative real-time PCR was carried out to detect deletions/insertions and rearrangements in 149 patients and 150 healthy controls. Results Four heterozygous mutations in PINK1 were identified, including 3 missense mutations (c.832C > G, c. 938C > T, c. 1 220G > A) and ex 3-8 del. A novel single nucleotide polymorphism (SNP) c. 899 + 18G > A and 14 reported SNPs were identified. Chi-square test showed that c. 189C >T and c. 960 - 5G > A had significant difference in the genotype frequencies and allele frequencies between the patients and the controls (for c. 189C > T genotype X ² = 21. 244, P < 0.0001; T allele X ²=24. 353, P < 0.0001, and for c. 960 - 5G > A genotype's X ² = 6. 524, P = 0.038; A allele X ² = 6.725, P = 0.0095 ). Conclusion About 3. 35% Chinese Han patients with EOP carry mutations in PINK1. Two SNPs c. 189C > T and c. 960 - 5G > A may contribute to the risk of EOP in Chinese Han people.