Abstract
Several genes have already been certified as causative genes in patients with autosomal recessive early-onset Parkinson’s syndrome with pyramidal tract signs, including ATP13A2, PLA2G6 and FBXO7. Variants in these three genes may also play roles in early-onset Parkinson’s disease (EOPD). In order to investigate the contribution of genetic variants in these three genes to Chinese sporadic EOPD patients, we screened 101 Chinese sporadic EOPD patients and 83 age- and sex-matched healthy controls using direct sequencing. Interpretation of those detected variants was performed based on the guidelines developed by the American College of Medical Genetics and Genomics (ACMG). Two missense variants, p.G360E and p.T733M, with “uncertain significance” classification were identified in the ATP13A2 gene and five synonymous variants were significantly over-represented in EOPD patients. Two missense variants, p.R53C and p.T319M, were absent in both our control group and online databases, classified as “likely pathogenic” in the PLA2G6 gene. Only benign variants were identified in the FBXO7 gene. These results indicate that rare variants of PLA2G6 may contribute to PD susceptibility in Chinese population, the ATP13A2 might be associated with higher risk for sporadic EOPD, while the FBXO7 gene doesn’t seem to be a risk factor to develop sporadic PD in Chinese population. Further biochemical and molecular biological studies needs to be conducted to support our main results in our future researches.
Highlights
Neuroaxonal dystrophy (INAD) and neurodegeneration with brain iron accumulation (NBIA)[11]
In the PLA2G6 gene, we found fourteen variants: (1) three missense variants all in heterozygous state (Fig. 1), (2) three synonymous variants, including p.L496L in exon 10 that hasn’t been reported previously, but doesn’t lead to amino acid change, (3) eight intron variants of intron/exon boundaries (Table 1)
In the FBXO7 gene, we found seven variants: (1) one missense variant in exon 2, c.345G > A (Fig. 1), (2) one synonymous variant in exon 6, p.L317L, (3) five intron variants of intron/exon boundaries, including c.1182 + 133A > G that hasn’t been detected (Table 1)
Summary
Neuroaxonal dystrophy (INAD) and neurodegeneration with brain iron accumulation (NBIA)[11]. Previous studies suggested that this gene was associated with juvenile-onset dystonia parkinsonism and classic idiopathic PD12–15. The FBOX7 (PARK15) gene encodes an E3 ligase, F-box only protein 7, which is involved in ubiquitin proteasome system[16] and mitochondrial maintenance[17]. Pathogenic variants in FBXO7 gene are likely to cause the EOPD in a similar way to the Parkin and PINK1 genes[17]. The involvements of these three genes in idiopathic sporadic PD pathogenesis are still unclear. We investigated the contribution of genetic variants in ATP13A2, PLA2G6 and FBXO7 to sporadic EOPD patients and complement the current research in China
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