Rare and novel variants of PRKN and PINK1 genes in Vietnamese patients with early‐onset Parkinson’s disease

• Published in: Molecular genetics & genomic medicine Vol. 8; no. 10; pp. e1463 - n/a
• Main Authors: Ton, Nguyen Dang, Thuan, Nguyen Duc, Thuong, Ma Thi Huyen, Ngoc, Tran Thi Bich, Nhung, Vu Phuong, Hoa, Nguyen Thi Thanh, Nam, Nguyen Hoai, Dung, Hoang Thi, Son, Nhu Dinh, Ba, Nguyen Van, Bac, Nguyen Duy, Tai, Tran Ngoc, Dung, Le Thi Kim, Hung, Nguyen Trong, Duong, Nguyen Thuy, Ha, Nguyen Hai, Hai, Nong Van
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01-10-2020; John Wiley and Sons Inc; Wiley
• Subjects: Age; Constipation; Disease; early‐onset Parkinson's disease; Genes; Genetic engineering; Genetic screening; Genomes; Genotypes; Hallucinations; Identification methods; Kinases; Metabolic pathways; Movement disorders; Mutation; Neurodegenerative diseases; Original; PARKIN; Parkin protein; Parkinson's disease; Patients; PINK1; Polymorphism; PTEN-induced putative kinase; Risk analysis; Risk factors; Signs and symptoms; Software; Vietnamese; Netherlands; Vietnam; United States > US; Massachusetts; Ho Chi Minh City Vietnam; early-onset Parkinson's disease; PARKIN; Vietnamese; PINK1
• ISSN: 2324-9269; 2324-9269
• DOI: 10.1002/mgg3.1463

Background
Early‐onset Parkinson's disease (EOPD) refers to that of patients who have been diagnosed or had onset of motor symptoms before age 50, accounting for 4% of Parkinson's disease patients. The PRKN and PINK1 genes, both involved in a metabolic pathway, are associated with EOPD.
Methods
To identify variants associated with EOPD, coding region of PARKIN and PINK1 genes in 112 patients and 112 healthy individuals were sequenced. Multiplex ligation‐dependent probe amplification kit was used to determine EOPD patients that carried mutations in PRKN and PINK1 genes.
Results and Conclusion
Three rare and three novel mutations in total of 14 variants of PARKIN and PINK1 were detected in the EOPD cohorts. Mutations of PRKN and PINK1 genes were found in five (4.4%) patients, which were four patients with compound heterozygous variants in the PRKN and one case with a homozygous mutation of the PINK1 gene. The novel mutations might reduce the stability of the PRKN and PINK1 protein molecules. The frequency of homozygous mutant genotype p.A340T of the PINK1 in the EOPD cohort was higher than in control (p = 0.0001, OR = 5.704), suggesting this variant might be a risk factor for EOPD. To the best of our knowledge, this is the first study of PRKN and PINK1 genes conducted on Vietnamese EOPD patients. These results might contribute to the genetic screening of EOPD in Vietnam.
To identify variants associated with Vietnamese EOPD, we performed sequence analysis of coding region of PARKIN and PINK1 in 112 patients and 112 healthy individuals. Three rare and three novel mutations in total of 14 variants of PARKIN and PINK1 were detected. The novel mutations might reduce the stability of the PRKN and PINK1 protein molecules.