Abstract
Recently, RAB39B mutations were reported to be a causative factor in patients with Parkinson’s disease (PD). To validate the role of RAB39B in familial PD, a total of 195 subjects consisting of 108 PD families with autosomal-dominant (AD) inheritance and 87 PD families with autosomal-recessive (AR) inheritance in the Chinese Han population from mainland China were included in this study. We did not identify any variants in the coding region or the exon-intron boundaries of the gene by Sanger sequencing method in the DNA samples of 180 patients (100 with AD and 80 with AR). Furthermore, we did not find any variants in the RAB39B gene when Whole-exome sequencing (WES) was applied to DNA samples from 15 patients (8 with AD and 7 with AR) for further genetic analysis. Additionally, when quantitative real-time PCR was used to exclude large rearrangement variants in these patients, we found no dosage mutations in RAB39B gene. Our results suggest that RAB39B mutation is very rare in familial PD and may not be a major cause of familial PD in the Chinese Han Population.
Highlights
Parkinson’s disease (PD) is a common late onset neurodegenerative disorder, clinically characterized by a series of motor symptoms and non-motor symptoms
We did not identify any variants in the RAB39B gene among the 195 familial PD patients by Sanger sequencing
Relative quantification by qRT-Polymerase chain reaction (PCR) showed that the relative copy number of RAB39B expression in our 195 PD individuals was between 0.8–1.2 in female PD patients and 0.45–0.6 in male PD patients, which meant that there were no dosage mutations in RAB39B gene among our familial PD patients
Summary
Parkinson’s disease (PD) is a common late onset neurodegenerative disorder, clinically characterized by a series of motor symptoms and non-motor symptoms. Previous studies reported that about 10% of the patients have a positive family history of PD and that a series of genes, such as SNCA, LRRK2, VPS35, Parkin, PINK1, and DJ-1, were associated with the disease[2]. The Threonine residue was shown to be evolutionarily-conserved[3] In another group, Mata et al reported a missense mutation, c.574G >A (p.Gly192Arg), in a North American family of European origin; the affected family members were characterized with a classical PD phenotype. Mata et al reported a missense mutation, c.574G >A (p.Gly192Arg), in a North American family of European origin; the affected family members were characterized with a classical PD phenotype This mutation was predicted to be deleterious as defined by Combined Annotation Dependent Depletion (CADD)[5]. To validate the role of the RAB39B gene in susceptibility to familial PD in the Chinese Han population, we conducted this study in 195 families consisting of PD patients with AD and AR inheritance, in whom the common causative genetic mutations, in genes such as SNCA, LRRK2, UCHL1, HtrA2, GIGYF2, EIGIF4, parkin, PINK1, DJ-1, ATP13A2, and PLA2G6, had previously been excluded[7,8,9]
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