National Laboratory of Medical Genetics of China

Changsha, China

National Laboratory of Medical Genetics of China

Changsha, China
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Guo J.-F.,Central South University | Wang L.,Central South University | He D.,Central South University | Yang Q.-H.O.,First Affiliated Hospital | And 6 more authors.
Neurological Sciences | Year: 2011

Mutations in the Parkin, PINK1, and DJ-1 genes can cause autosomal recessive early onset Parkinsonism. We studied three families with the mutations of the Parkin, PINK1 and DJ-1 genes, respectively, with a dopamine transporter ligand [11C]-CFT positron emission tomography. A marked bilaterally and dissymmetrically decrement of [11C]-CFT uptake was found in all these patients, and putamen as well as caudate nucleus was affected. We also found asymptomatic Parkin and PINK1 heterozygotes showed a mild but significant decrement in [11C]-CFT uptake, but this phenomenon was not found in the DJ-1-heterozygotes. Our results suggested the three autosomal recessive forms of early onset are similar to each other on pathophysiological grounds, a sub-clinical disease process in Parkin and PINK1-heterozygotes, but not in DJ-1-heterozygotes. © 2010 Springer-Verlag.


Liu J.,Central South University | Sun Q.-Y.,Central South University | Tang B.-S.,Central South University | Tang B.-S.,National Laboratory of Medical Genetics of China | And 8 more authors.
Brain Research | Year: 2011

Genetic variants of PITX3 gene have been reported to be associated with Parkinson's disease (PD) in several populations. We conducted a case-control study and genotyped the three SNPs of PITX3 gene: rs2281983, rs4919621 and rs3758549 in 512 mainland Chinese PD patients and 506 healthy controls. Our findings show that the PITX3 gene rs3758549 polymorphism is associated with PD (p = 0.02). Moreover, the difference between late onset PD patients and healthy controls is stronger (p = 0.007). There is no statistical difference in genotype or allele frequencies of rs2281983 or rs4919621 variant in PITX3 gene between sporadic PD (SPD) group and healthy control group in our study. To assess the possible role of the PITX3 gene rs3758549 polymorphism in PD, we conducted a meta-analysis on the topic. The results of meta-analysis further support that the PITX3 gene rs3758549 polymorphism is associated with PD: Z = 3.09, p = 0.002, OR = 0.89. These findings suggest that the PITX3 gene rs3758549 polymorphism may increase the susceptibility of PD. © 2011 Elsevier B.V.


Wang C.-Y.,Central South University | Xu Q.,Central South University | Weng L.,Central South University | Zhang Q.,Central South University | And 7 more authors.
Brain Research | Year: 2011

Parkinson's disease (PD) is the second most common neurodegenerative disorder, with approximately 5-10% of PD cases being linked to genetic factors. The Htra serine peptidase 2 (HTRA2) gene, also known as Omi, was found to be associated with PD in a cohort of German PD patients. However, subsequent studies have indicated that some variants of Omi/HTRA2 may not be related to PD. In order to investigate whether the Omi/HTRA2 gene is related to PD in Han Chinese PD patients, molecular analysis for the Omi/HTRA2 gene was performed in 404 Chinese PD patients and 504 normal individuals. Our present study revealed 2 novel variations. The IVS5 + 29T > A variant may be a risk factor for PD (P < 0.05), while the c.G77A variant might be a pathogenic mutation. However, the findings need to be validated in a larger population using further functional studies. © 2011 Elsevier B.V.


Sun Q.-Y.,Central South University | Guo J.-F.,Central South University | Wang L.,Central South University | Yu R.-H.,Central South University | And 6 more authors.
Movement Disorders | Year: 2010

An association between mutations in the glucocerebrosidase (GBA) gene and Parkinson's disease (PD) has been reported in several populations. We searched for four common GBA mutations (L444P, F213I, R353W, and N370S) in 402 Chinese PD patients and 413 age- and sex-matched controls. In the PD cohort, 11 patients were found carrying a heterozygous GBA mutation and all of them had the L444P mutation. Heterozygous GBA mutations were detected none in controls. The GBA gene L444P mutation was detected at a significantly higher frequency among PD patients (11/402 = 2.74%), when compared with the control group (0/413): P 5 0.0007. To evaluate the possible role of the GBA gene L444P mutation in PD in Ashkenazi Jewish and non-Jewish populations, we conducted a meta-analysis on the topic. In the Chinese population, the GBA gene L444P mutation was detected at a significantly higher frequency among PD patients, when compared with the control group: Z = 3.83, P = 0.0001, OR = 8.42, confidence interval = 95%, 2.83-25.06. In the non-Jewish populations, the difference was obviously significant: Z = 5.76, P < 0.00001, OR = 8.82, confidence interval = 95%, 4.21-18.48. The results suggest that the GBA gene L444P mutation appears to be a risk factor for PD in Chinese population. © 2010 Movement Disorder Society.


Zhang B.-R.,Zhejiang University | Tian J.,Zhejiang University | Yan Y.-P.,Zhejiang University | Yin X.-Z.,Zhejiang University | And 5 more authors.
Journal of the Neurological Sciences | Year: 2012

Huntington's disease (HD) is caused by the abnormal expansion of CAG repeats in the huntingtin gene (HTT). The adjacent proline-rich region, which also has a CCG polymorphism among people of different races, may also affect the pathogenesis of HD. To study the effect of this polymorphism on patients with HD in mainland China, 53 HD mutant alleles were examined. The results showed that 54.72% of the HD mutant alleles had 10-repeat alleles, and the remaining 45.28% had 7-repeat alleles. Moreover, comparison of the clinical features between the two groups revealed no significant difference. We also investigated its effect on the aggregates in vitro. No significant difference was detected when the morphology and size of the aggregates with the two polymorphisms was compared in cells. Given these findings, it was quite reasonable to suppose that the CCG polymorphism may not influence the pathogenesis of patients with HD in mainland China. © 2011 Elsevier B.V.


Shi C.-H.,Central South University | Tang B.-S.,Central South University | Tang B.-S.,National Laboratory of Medical Genetics of China | Wang L.,Central South University | And 9 more authors.
Neurology | Year: 2011

Objective: Mutations in the PLA2G6 gene at the PARK14 locus have been reported in complicated parkinsonism. To assess the prevalence of and phenotypes associated with PLA2G6 gene mutations, we screened PLA2G6 mutations in a cohort of patients with autosomal recessive early-onset parkinsonism (AREP). Methods: We selected 12 families with AREP in which the Parkin, PINK1, DJ-1, ATP13A2, and FBXO7 gene mutations had been previously excluded. All patients came from the mainland of China. The entire PLA2G6 coding region and exon-intron boundaries were sequenced from genomic DNA templates. We then performed PET studies on individuals in the pedigree with a homozygous PLA2G6 mutation, and investigated the enzyme activity level of the mutation. Results: A homozygous missense mutation, c.G991T (p.D331Y), was identified in an autosomal recessive case. A younger sister of the p.D331Y-carrying patient was also homozygous for the mutation, but with no extrapyramidal symptoms. A PET study showed a substantial reduction in dopamine transporter (DAT) binding in the p.D331Y patient, and a slight reduction in DAT binding in his sister. In vitro, we experimentally demonstrate that the D331Y mutation caused an approximately 70%reduction in enzyme activity. Conclusions: We have confirmed that the PLA2G6 gene allocated PARK14 locus and is associated with AREP. Copyright © 2011 by AAN Enterprises, Inc.


Guo J.-F.,Central South University | Zhang X.-W.,Central South University | Nie L.-L.,Central South University | Zhang H.-N.,Central South University | And 6 more authors.
Journal of Neurology | Year: 2010

Early onset parkinsonism (EOP) has been associated with mutations in the Parkin, PINK1, and DJ-1 genes. We studied the prevalence of mutations in all three genes in 127 unrelated Chinese patients with apparently sporadic EOP using direct sequencing analysis and real-time quantitative PCR analysis assay. There are 16 patients (12.6%) with mutations of Parkin gene, four patients (3.1%) with mutations of PINK1 gene, and three patients (2.4%) with mutation of DJ-1 gene. In conclusion, Parkin gene mutation is the most common pathogenic factor in Chinese patients with sporadic EOP. Mutations of DJ-1 and PINK1 gene are also found in Chinese patients with sporadic EOP. © 2010 Springer-Verlag.


Yuan X.-L.,Central South University | Guo J.-F.,Central South University | Shi Z.-H.,Academia Sinica, China | Shi Z.-H.,Hebei Normal University | And 5 more authors.
Brain Research | Year: 2010

The identification of rare monogenic forms of Parkinson's disease (PD) has provided tremendous insights into the molecular pathogenesis of the disorder. Mitochondrial dysfunction and oxidative stress are thought to play a prominent role in the pathogenesis of PD, but how the monogenic mutation gene causes the disease onset or progression is largely unknown. In this study we investigated the effects of wild-type and R492X mutation in the PTEN-induced putative kinase 1 (PINK1). Cell cultures show that R492X PINK1 mutation induces the generation of cellular reactive oxidative species (ROS), degrades cell membrane potential, causes cytochrome C (Cyt.C) release from mitochondrial to cytoplasm, attenuates mitochondrial complex I activity, and lastly, causes changes in mitochondrial numbers and morphology; especially when cells are treated with 1-Methyl-4-phenylpyridinium ion (MPP+). Our results suggest that the R492X mutation can cause mitochondrial dysfunction and oxidative stress and can associate with MPP+ to induce mitochondrial dysfunction and oxidative stress. © 2010 Elsevier B.V.


Hu Y.,Central South University | Tang B.,Central South University | Tang B.,National Laboratory of Medical Genetics of China | Guo J.,Central South University | And 10 more authors.
Journal of Neurology | Year: 2012

Parkinson's disease (PD) is the second most common neurodegenerative disorder. The presence of Lewy bodies is a major pathological change of PD. α-synuclein is the main component of Lewy bodies and is encoded by the SNCA gene. Mutations in the SNCA gene mainly result in rare familial forms of PD, while genetic variability in the SNCA gene modulates susceptibility to sporadic PD. Recent studies have suggested that levels of α-synuclein in extracellular biological fluid are associated with PD and implicated α-synuclein as a potential biomarker for PD diagnosis and severity. We studied serum α-synuclein concentration and two polymorphic variants of SNCA (Rep1 and rs11931074) in 110 sporadic PD patients and 136 controls. We further explored the influence of the two polymorphisms on the expression levels of serum α-synuclein. Soluble α-synuclein was detected in serum in all subjects, with no statistically significant difference between PD patients and controls (p = 0.611). Different Rep1 alleles and genotypes did not influence the expression of serum α-synuclein. The frequency of allele T of rs11931074 was significantly elevated in PD patients (p = 0.041), and was correlated with decreased serum α-synuclein in both dominant (p = 0.011) and additive (p = 0.008) models of association. © Springer-Verlag 2011.


He Y.,Central South University | He Y.,The Second Affiliated Hospital of XinXiang Medical College | Xun G.,Central South University | Xia K.,National Laboratory of Medical Genetics of China | And 4 more authors.
Psychiatry Research | Year: 2011

The present study genotyped four SNPs (rs736707, rs2229864, rs362691, and rs2073559) of the Reelin gene (RELN) in 165 autistic trios, 67 sporadic autistic children and 283 healthy controls with Chinese Han pedigree. Both case-control analysis and transmission disequilibrium test (TDT) found no evidence of significant association. The results do not support previous positive findings and suggest that the four single-nucleotide polymorphisms (SNP) of RELN are unlikely to be associated with childhood autism in Chinese Han population. © 2010 Elsevier Ltd.

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