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

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• 作者：Ekaterina Yonova-Doing^a ; Masharip Atadzhanov^b ; ^{masharip@yahoo.com} ; Marialuisa Quadri^a ; Paul Kelly^b ; Nyambura Shawa^b ; Sheila T.S. Musonda^b ; Erik J. Simons^a ; Guido J. Breedveld^a ; Ben A. Oostra^a ; Vincenzo Bonifati^a ; ^{v.bonifati@erasmusmc.nl}
• 关键词：Parkinson's disease ; Zambia ; Genetics ; SNCA ; LRRK2 ; Parkin ; PINK1 ; DJ-1
• 刊名：Parkinsonism and Related Disorders
• 出版年：2012
• 期刊代码：215_13538020
• 类别：med
• 出版时间：June, 2012
• 卷：18
• 期：5
• 页码：567-571
• 文件大小：495 K

摘要

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聽卤聽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聽=聽22) the whole LRRK2 coding region was sequenced (51 exons). In the patients with onset <50 years (n聽=聽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.