Analysis of LRRK2, SNCA, Parkin, PINK1, and DJ-1 in Zambian patients with Parkinson's disease

作者：Yonova Doing Ekaterina; Atadzhanov Masharip; Quadri Marialuisa; Kelly Paul; Shawa Nyambura; Musonda Sheila T S; Simons Erik J; Breedveld Guido J; Oostra Ben A; Bonifati Vincenzo^*

来源：Parkinsonism & Related Disorders, 2012, 18(5): 567-571.

DOI：10.1016/j.parkreldis.2012.02.018

• Parkinson's disease
• Zambia
• Genetics
• SNCA
• LRRK2
• Parkin
• PINK1
• DJ-1

Recent studies delineate substantial genetic components in Parkinson's disease (PD). However, very few studies were performed in Sub-Saharan African populations. Here, we explore the contribution of known PD-causing genes in patients of indigenous Zambian ancestry. We studied thirty-nine Zambian patients, thirty-eight with PD and one with parkinsonian-pyramidal syndrome (18% familial: average onset age 54.9 +/- 12.2 years). In the whole group, all SNCA exons and LRRK2 exons 29 to 48 (encoding for important functional domains) were sequenced. In the familial patients and those with onset < 55 years (n = 22) the whole LRRK2 coding region was sequenced (51 exons). In the patients with onset < 50 years (n = 12), all parkin, PINK1, and DJ-1 exons were sequenced, and dosage analysis of parkin, PINK1, DJ-1, LRRK2, and SNCA was performed. Dosage analysis was also performed in the majority of the late-onset patients.
The LRRK2 p.Gly2019Ser mutation was not detected. A novel LRRK2 missense variant (p.Ala1464Gly) of possible pathogenic role was found in one case. Two heterozygous, likely disease-causing deletions of parkin (exon 2 and exon 4) were detected in an early-onset case. Pathogenic mutations were not detected in SNCA, PINK1, or DJ-1. We also report variability at several single nucleotide polymorphisms in the above-mentioned genes.
This is the first molecular genetic study in Zambian PD patients, and the first comprehensive analysis of the LRRK2 and SNCA genes in a Sub-Saharan population. Common disease-causing mutations were not detected, suggesting that further investigations in PD patients from these populations might unravel the role of additional, still unknown genes.

• 出版日期2012-6