Zhi Song

The Third Xiangya Hospital of the Central South University, Ch’ang-sha-shih, Hunan, China

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Publications (50)108.55 Total impact

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    ABSTRACT: Limb-girdle muscular dystrophies (LGMD) are a highly heterogeneous group of genetic myopathies characterized by progressive proximal pelvic and/or shoulder girdle muscle weakness, with the onset ages ranging from early childhood to late adulthood. The identification of these dystrophies through genetic testing will not only inform long-term prognosis but will also assist in directing care more efficiently, including more frequent cardiorespiratory monitoring and prophylactic treatments. The aim of this study was to identify the responsible gene in a five-generation Chinese Han pedigree with autosomal recessive LGMD. Exome sequencing was conducted and a novel mutation c.107788T>C (p.W35930R) in the titin gene (TTN) was identified. The mutation co-segregated with the disorder in the family and was absent in normal controls. Our discovery broadens the mutation spectrum of the TTN gene associated with LGMD2J.
    Molecular Neurobiology 09/2015; DOI:10.1007/s12035-015-9439-0 · 5.14 Impact Factor
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    ABSTRACT: To examine the association between the sphingomyelin phosphodiesterase 1, acid lysosomal (SMPD1) gene, and Parkinson's disease (PD) in Han Chinese from Central South part of Mainland China, we performed systematic genetic analysis in 502 Chinese Han patients with PD and 637 gender-, age-, and ethnicity-matched normal controls from Central South part of the Mainland China. We identified 11 single nucleotide variants and Leu-Ala (Val) repeat variants in the SMPD1 gene in our large cohort. Two novel missense variants, c.638A > C (p.H213P) and c.1673T > C (p.L558P), and a rare known missense variant, c.1805G > A (p.R602H, rs370129081), were identified in three sporadic PD cases. None of these three variants were observed in controls. Additionally, case-control analysis showed association between Leu-Ala (Val) repeat variants in SMPD1 and Chinese Han patients with PD (P = 0.015, χ (2) = 8.451). Our data provide supportive evidence that some genetic variants in SMPD1 increase the risk of PD in the Chinese Han population.
    Molecular Neurobiology 09/2015; DOI:10.1007/s12035-015-9426-5 · 5.14 Impact Factor
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    ABSTRACT: A number of studies have suggested that the Cyclin D1 (CCND1) G870A polymorphism was associated with susceptibility to various cancers. In the present study, we aimed to investigate the association between CCND1 G870A polymorphism and the risk of glioma in a Chinese population. CCND1 genotyping was determined by the PCR-RFLP method. The χ (2) test was used to assess for any deviation of the genotype frequencies from Hardy-Weinberg equilibrium and to compare the genotype distributions among glioma patients and healthy control subjects. We calculated the odds ratios (ORs) and 95% confidence intervals (95% CIs) by using unconditional logistic regression. The A allele frequency was higher in cases than that in controls (49.40% vs. 36.39%), and this difference was statistically significant (P = 0.001). Using the G allele as the reference allele, the subjects carrying the A allele had 3.926-fold increase in the risk of glioma (95% CI, 2.172-7.889), and p-value was significant (P = 0.007). Compared to individuals with the GG genotype, individuals with the AA genotype exhibited significantly increased glioma risk (OR = 3.661, 95% CI: 1.658-6.287, P = 0.01). Our results suggest that the CCND1 G870A polymorphism may contribute to the susceptibility to glioma in Chinese population.
    International Journal of Clinical and Experimental Medicine 08/2015; 8(6):9991-5. · 1.28 Impact Factor
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    ABSTRACT: Ischemic stroke (IS) is a multifactorial disease that displays a strong genetic predisposition. However, the genetic architecture of IS has yet to be fully elucidated. It was hypothesized that epistasis between genes in multiple atherothrombotic pathways may play a vital role in determining the susceptibility to IS. The aim of the present study was to investigate the contributions of the hypothesized genetic factors to IS and the interactions between these genetic factors in a Chinese population. In this study, 351 cases with IS and 417 control subjects from a Chinese population were genotyped for single-nucleotide polymorphisms (SNPs) in 12 genes hypothesized to be involved in atherosclerosis, coagulation, and related pathways. We examined SNP main effects and epistatic interactions between these polymorphic loci. rs710446 of the KNG1 gene was associated with IS susceptibility based on an additive genetic model (rs710446: P = .012; odds ratio [OR], 1.247; 95% confidence interval [CI], 1.050-1.481) after adjusting for covariates. Furthermore, an epistatic interaction between the ALOX5AP, THBD, and KNG1 gene was also identified in association with stroke susceptibility (P < .001 after 1000 permutations). Based on the chi-squared test, the OR of the high-risk combination of the three-locus model increased the risk of IS by 2.53-fold (95% CI, 1.60-4.01; P < .0001). Our findings support the association of the epistatic interactions of ALOX5AP, THBD, and KNG1 and present novel evidence for the main effect of KNG1 gene on IS susceptibility, suggesting a modulation of stroke risk by a genetic main effect and gene-gene interactions. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.
    Journal of stroke and cerebrovascular diseases: the official journal of National Stroke Association 07/2015; 24(9). DOI:10.1016/j.jstrokecerebrovasdis.2015.04.036 · 1.67 Impact Factor
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    ABSTRACT: Parkinson's disease (PD) is a common neurodegenerative disorder of complex etiology. Mounting evidence indicates that genetic abnormalities play an important role in the pathogenesis of PD. To date, at least 20 genetic loci and 15 disease-causing genes for parkinsonism have been identified, as well as some susceptibility genes conferring risk to PD. More recently, mutations in the RAB39B gene (RAB39B, member RAS oncogene family) have been reported to cause X-linked intellectual disability and early-onset PD with α-synuclein pathology. To evaluate whether variants in the RAB39B gene are related to PD in Chinese Han population, we conducted genetic analysis of the RAB39B gene in 502 patients with PD from Mainland China. No pathogenic mutation or variant was identified in the coding region or exon-intron boundaries of the gene. Our results suggest that mutation(s) in the coding region of the RAB39B gene plays little or no role in the development of PD in Chinese population. Copyright © 2015 Elsevier Inc. All rights reserved.
    Neurobiology of aging 06/2015; 36(10). DOI:10.1016/j.neurobiolaging.2015.06.019 · 5.01 Impact Factor
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    ABSTRACT: This paper was designed to investigate anticonvulsant and sedative effects of eudesmin isolated from Acorus tatarinowii. The eudesmin (5, 10, and 20 mg/kg) was administered intraperitoneally (i.p.). The maximal electroshock test (MES) and pentylenetertrazole (PTZ)-induced seizures in male mice were used to evaluate anticonvulsant activities of eudesmin, and sedative effects of eudesmin were evaluated by pentobarbital sodium-induced sleeping time (PST) and locomotor activity in mice. Finally, the mechanisms of eudesmin were investigated by determining contents of glutamic acid (Glu) and gamma-aminobutyric acid (GABA) in epileptic mice, and expressions of glutamate decarboxylase 65 (GAD65), GABAA , Bcl-2, and caspase-3 in the brain of chronic epileptic rats. Results of MES and PTZ tests revealed that eudesmin possesses significant anticonvulsant effects, and the PST and locomotor activity tests demonstrated that eudesmin has significant sedative effects. Furthermore, our study revealed that after treatment with eudesmin, GABA contents increased, whereas Glu contents decreased, and ratio of Glu/GABA decreased. Our results also indicated that expressions of GAD65, GABAA, and Bcl-2 were up-regulated by treating with eudesmin, whereas the caspase-3 obviously was down-regulated. In conclusion, eudesmin has significant anticonvulsant and sedative effects, and the mechanism of eudesmin may be related to up-regulation of GABAA and GAD65 expressions, and anti-apoptosis of neuron the in brain. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.
    Phytotherapy Research 04/2015; 29(7). DOI:10.1002/ptr.5337 · 2.66 Impact Factor
  • Ru Chen · Zelin Deng · Zhi Song
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    ABSTRACT: Malignant middle cerebral artery infarction (MMI) is always associated with high mortality rates. Early decompressive craniectomy is crucial to its treatment. The purpose of this study was to establish a reliable model for an early prediction of MMI. Using a retrospective survey, we have collected the data of 132 patients with middle cerebral artery infarction. According to a prognosis, the patients are divided into the MMI group (n = 36) and the non-MMI group (n = 96). All the patients are represented by their clinical, biochemical, and imaging features. Then a random forest (RF) prediction model is established on the clinical data. Meanwhile, 3 traditional prediction models, including univariate linear discriminant analysis (LDA) model, multivariate LDA model, and binary logistic regression analysis (BLRA), are built to compare with the RF model. The prediction performance of different models is assessed by the area under the receiver operating characteristic curves (AUCs). Four parameters, Glasgow Coma Scale, midline shifting, area, and volume of focus, selected as predictors in all models. As independent predictors, their AUCs are .72-.80, and when the sensitivities are high (.91-.95), the specificities are low (.32-.53). The AUC of RF model is .96, 95% confidence interval (CI) is (.93-.99), sensitivity is 1, and specificity is .85. The AUC of the multivariate LDA model is .87 and 95% CI is (.80-.93). The AUC of the BLRA model is .86 and 95% CI is (.80-.93). The RF performs very well in the given clinical data set, which indicates that the RF is applicable to the early prediction of the MMI. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.
    Journal of stroke and cerebrovascular diseases: the official journal of National Stroke Association 03/2015; 24(5). DOI:10.1016/j.jstrokecerebrovasdis.2014.12.016 · 1.67 Impact Factor
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    ABSTRACT: Febrile seizures (FS), the most frequent type of seizures in children, occur in neurologically normal infants and children between the ages of 3 months and 5 years with genetic predisposition. The aim of this study was to identify the responsible gene in a four-generation Chinese Han pedigree with autosomal dominant FS. Seven family members (three affected and four unaffected) were enrolled in this study. Exome sequencing was conducted and a duplication mutation c.649dupC (p.R217Pfs*8) in the proline-rich transmembrane protein 2 gene (PRRT2) was identified. The mutation co-segregated with the disorder and was absent in normal controls. To our knowledge, this is the first report of a pedigree with complete penetrance of FS, which is caused by mutation in the PRRT2 gene. FS is a novel phenotype of the c.649dupC (p.R217Pfs*8) mutation. Our discovery broadens the spectrum of genetic causes of FS and the spectrum of phenotypes linked to mutation in the PRRT2 gene.
    Molecular Neurobiology 12/2014; DOI:10.1007/s12035-014-9047-4 · 5.14 Impact Factor
  • Yu Liu · Huarong Yang · Zhi Song · Shaojuan Gu
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    ABSTRACT: Copper is an essential trace element that serves as an important catalytic cofactor for cuproenzymes, carrying out major biological functions in growth and development. Although Wilson's disease (WD) is unquestionably caused by mutations in the ATP7B gene and subsequent copper overload, the precise role of copper in inducing pathological changes remains poorly understood. Our study aimed to explore, in HepG2 cells exposed to copper, the cell viability and apoptotic cells was tested by MTT and Hoechst 33342 stainning respectively, and the signaling pathways involved in oxidative stress response, apoptosis and lipid metabolism were determined by real time RT-PCR and Western blot analysis. The results demonstrate dose- and time-dependent cell viability and apoptosis in HepG2 cells following treatment with 10μM , 200μM and 500μM of copper sulfate for 8 and 24 h. Copper overload significantly induced the expression of HSPA1A (heat shock 70kDa protein 1A), an oxidative stress-responsive signal gene, and BAG3 (BCL2 associated athanogene3), an anti-apoptotic gene, while expression of HMGCR (3-hydroxy-3-methylglutaryl-CoA reductase), a lipid biosynthesis and lipid metabolism gene, was inhibited. These findings provide new insights into possible mechanisms accounting for the development of liver apoptosis and steatosis in the early stages of Wilson's disease.
    The Turkish journal of gastroenterology: the official journal of Turkish Society of Gastroenterology 12/2014; 25(Suppl 1):S116-S121. DOI:10.5152/tjg.2014.5064 · 0.78 Impact Factor
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    ABSTRACT: Trans-caryophyllene (TC), a component of essential oil found in many flowering plants, has shown its neuroprotective effects in various neurological disorders. However, the effects of TC on epilepsy haven't been reported before. In this study, we investigated the effect of TC on kainic acid-induced seizure activity caused by oxidative stress and pro-inflammation. We found that TC pretreatment significantly decreased seizure activity score compared to kainic acid treated group. Importantly, TC pretreatment leads to lowering the mortality in kainic acid treated mice. In addition, TC was found to significantly inhibit KA-induced generation of malondialdehyde. TC pretreatment also preserved the activity of GPx, SOD, and CAT. Notably, our data shows that an important property of TC is its capacity to exert cerebral anti-inflammatory effects by mitigating the expression of proinflammatory cytokines, such as TNF-α and IL-1β. These data suggest that TC has a potential protective effect on chemical induced seizure and brain damage.
    Neurochemical Research 11/2014; 40(1). DOI:10.1007/s11064-014-1474-0 · 2.59 Impact Factor
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    ABSTRACT: Recent studies have demonstrated the protective effect of mitochondrial aldehyde dehydrogenase 2 (ALDH2) in cardiovascular diseases. Increased levels of the potential ALDH2 substrate 4-hydroxynonenal (4-HNE) are involved in myocardial/cerebral ischemia accompanied by a high level of oxidative stress. In this investigation, we first performed a case-control study to explore the potential association of ALDH2 rs671 polymorphism and post-stroke epilepsy (PSE). Then, we performed an in vitro study to determine whether the overexpression of ALDH2 could decrease the level of oxidative stress and the apoptosis ratio induced by 4-HNE. There was a significant difference in the distribution of the allele and genotype frequencies of the rs671 polymorphism between PSE patients and ischemic stroke (IS) patients. Individuals with the rs671 A allele showed significantly higher levels of plasma 4-HNE. The overexpression of ALDH2 partially blocked the increased levels of malondialdehyde (MDA), reactive oxygen species (ROS) and apoptosis ratio induced by 4-HNE and also partially restored the ALDH2 activity in PC12 cells; these effects were reversed in the presence of εV1-2. Our results suggest that the ALDH2 rs671 polymorphism is associated with PSE susceptibility and affects the 4-HNE levels. Targeting ALDH2 might be a useful strategy for the treatment or prevention of PSE.
    PLoS ONE 10/2014; 9(10):e109634. DOI:10.1371/journal.pone.0109634 · 3.23 Impact Factor
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    ABSTRACT: Background: Stroke is one of the main causes of death and adult chronic disability. Recently, 2 independent genome-wide association studies reported that the genetic variants (rs556621 and rs11984041) are significantly associated with large artery atherosclerosis (LAA). Methods: To determine whether these 2 variants are associated with the pathogenesis of LAA in stroke patients from the Xinjiang Uyghur autonomous region of China, both variants were evaluated in a series of 733 LAA stroke patients (434 Han and 299 Uyghur) and 725 age-, gender-, smoking-, alcohol habits- and ethnicity-matched controls (401 Han and 324 Uyghur). Results: For rs556621, significant differences in genotypic and allelic distributions were observed between Uyghur patients and controls (P = .045 for genotypic distribution, P = .042 for allelic distribution) but not in the Chinese Han cohort (P > .05). No significant differences were found in genotypic and allele distributions between patients and controls for rs11984041 in either the Chinese Han or Uyghur cohort (P > .05). Conclusions: The variant rs556621 but not rs11984041 may increase susceptibility of LAA stroke in the Xinjiang Uyghur population.
    Journal of stroke and cerebrovascular diseases: the official journal of National Stroke Association 10/2014; 23(10). DOI:10.1016/j.jstrokecerebrovasdis.2014.06.015 · 1.67 Impact Factor
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    ABSTRACT: Parkinson disease (PD) is the second most common progressive neurodegenerative disorder. It is characterized by selective loss of dopamine-producing neurons and aggregation of alpha-synuclein (SNCA) in neurons of particular brain regions. At least 20 loci and 15 disease-causing genes have been identified. Rare missense or multiplication mutations in the SNCA gene have been reported to be involved in some familial and sporadic cases of PD. More recently, two novel pathogenic missense mutations (p.H50Q and p.G51D) were identified in the SNCA gene. To evaluate whether mutation(s) in the coding region of SNCA gene is related to PD in Chinese population, we investigated the SNCA gene in 502 PD patients of Chinese Han ethnicity from Mainland China. No pathogenic mutation was identified in the coding region of the gene. A known G to A transition (c.306 + 66G>A, rs10005233) in the intron 4, which does not potentially change splicing, was identified. Our data indicate that mutations in the coding region of the SNCA gene are not likely to be a common cause of PD in Chinese population.
    Acta neurologica Belgica 08/2014; 115(3). DOI:10.1007/s13760-014-0347-2 · 0.89 Impact Factor
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    ABSTRACT: Infantile nystagmus (IN) is characterized by bilateral involuntary, periodic, and predominantly ocular oscillations. In this article, we describe a mutation screen conducted on a 4-generation family in which 4 patients were affected with X-linked IN (XLIN). Experimental study. A 4-generation Chinese Han family including 4 symptomatic members with IN and 200 normal male controls. DNA was extracted from peripheral blood, and the FERM domain-containing 7 gene (FRMD7) was amplified on DNA samples of all the available family members. The mutation screen was conducted by performing direct DNA sequencing. A nonsense mutation (R335X) in the FRMD7 gene was identified in 4 male patients and an asymptomatic female member. Although the R335X mutation in the FRMD7 gene has been previously described, the clinical features, including both disease penetrance and severity, among individuals with FRMD7 mutation in our family vary greatly. One female member with the heterozygous R335X mutation had no clinical manifestation of the disease. This incomplete penetrance suggests that random X-chromosome inactivation may play a role in the pathogenesis of IN, and that loss of functional FRMD7 may account for the development of this disorder. Our findings may be helpful in the genetic counseling of patients with nystagmus.
    Canadian Journal of Ophthalmology 02/2014; 49(1):50-3. DOI:10.1016/j.jcjo.2013.09.001 · 1.33 Impact Factor
  • Hao Deng · Wen Zheng · Zhi Song
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    ABSTRACT: Epilepsy is a common and diverse set of chronic neurological disorders characterized by spontaneous, unprovoked, and recurrent epileptic seizures. Environmental factors and acquired disposition are proposed to play a role to the pathogenesis of epilepsy. Genetic factors are important contributors as well. Comparing to the phenotype of epilepsy caused by mutation of single gene on an autosome, the phenotype of X-linked epilepsy is more complex. X-linked epilepsy usually manifests as part of a syndrome or epileptic encephalopathy, and the variability of clinical manifestations of X-linked epilepsy may be attributed to several factors including the type of genetic mutation, methylation, X chromosome random inactivation, and mosaic distribution. As a result, it is difficult to establish the genotype-phenotype correlation, diagnostic tests, and genetic counseling. In this review, we provide an overview of the X-linked epilepsy including responsible loci and genes, the molecular biology, the associated complex phenotypes, and the interference factors. This information may provide us a better understanding of the pathogenesis of X-linked epilepsy and may contribute to clinical diagnosis and therapy of epilepsy.
    Molecular Neurobiology 11/2013; 49(3). DOI:10.1007/s12035-013-8589-1 · 5.14 Impact Factor
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    ABSTRACT: Objective: To determine the effect of Parkinson's disease-weight bearing exercise for better balance (PD-WEBB) exercise on balance impairment and falls in people with Parkinson's disease (PD). Methods: A single-blind, randomized controlled clinical trial was conducted. The falls efficacy scale score, unified Parkinson disease rating scale (UPDRS) score and Mini-BESTest score were measured and compared between a PD-WEBB group and a control group. Results: The falls efficacy scale score, UPDRS-2 score, UPDRS-3 score and Mini-BESTest score were improved in the PD-WEBB group compared with the control group (P<0.05), with no significant change in UPDRS-1 score between the two groups. Conclusion: PD-WEBB training can significantly improve the balance impairment and quality of life to prevent falls. PD-WEBB training is suitable for PD patients in China, and is a reasonable, effective and sustainable training of family and community assessment model.
    Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences 11/2013; 38(11):1172-1176. DOI:10.3969/j.issn.1672-7347.2013.11.015
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    ABSTRACT: There is growing evidence that genetic abnormalities play an important role in the pathogenesis of Parkinson disease (PD). At least 18 genetic loci and 13 disease-related genes for parkinsonism have been identified. The S100 calcium-binding beta (S100B), which is expressed and secreted by astrocytes, has been found to be associated with PD. To evaluate whether the S100B variants are related to PD in Chinese Han population, we conducted genetic examination of the S100B gene in 502 PD patients from Mainland China. We did identify two known variants c.279+4T>C (rs187503470) and c.99C>G (p.Leu33Leu, rs1051169) in our patients. Neither of these two variants is predicted to change amino acid or splice site, indicating that they are not pathogenic mutations. Our results suggest that mutations in the coding region or intron/exon boundaries of the S100B gene play little or no role in the development of PD in Chinese population.
    Neuroscience Letters 10/2013; 555:134-136. DOI:10.1016/j.neulet.2013.09.037 · 2.03 Impact Factor
  • Kai Gao · Wen Zheng · Xiong Deng · Wei Xiong · Zhi Song · Yan Yang · Hao Deng
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    ABSTRACT: Exome sequencing in a large essential tremor (ET) family identified a novel nonsense mutation (p.Q290X) in the fused in sarcoma gene (FUS) as the cause of this family. Because of the clinical overlap between ET and Parkinson's disease (PD), the role of FUS in an independent cohort of PD patients from China mainland was evaluated. The entire coding region of FUS in 508 Chinese Han patients with PD and the identified variants in 633 normal controls were evaluated. A variant was further screened in an additional 382 controls for the frequency in our population. A novel variant c.696C > T (p.Y232Y) in 2 sporadic patients with PD and six variants (c.52C > A, p.P18T; c.52C > T, p.P18S; c.147C > A, p.G49G; c.291C > T, p.Y97Y; c.684C > T, p.G228G; c.1176G > A, p.M392I) without significant difference in genotypic and allelic distributions in our PD cohort were identified. The FUS gene is not a genetic risk factor for PD in the population of Chinese Han ethnicity.
    Parkinsonism & Related Disorders 09/2013; 20(1). DOI:10.1016/j.parkreldis.2013.09.010 · 3.97 Impact Factor
  • Hao Deng · Xiaofei Xiu · Zhi Song
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    ABSTRACT: Epilepsy is one of the most common neurological disorders characterized by abnormal electrical activity in the central nervous system. The clinical features of this disorder are recurrent seizures, difference in age onset, type, and frequency, leading to motor, sensory, cognitive, psychic, or autonomic disturbances. Since the discovery of the first monogenic gene mutation in 1995, it is proposed that genetic factor plays an important role in the mechanism of epilepsy. Genes discovered in idiopathic epilepsies encode for ion channel or neurotransmitter receptor proteins, whereas syndromes with epilepsy as a main feature are caused by genes that are involved in functions such as cortical development, mitochondrial function, and cell metabolism. The identification of these monogenic epilepsy-causing genes provides new insight into the pathogenesis of epilepsies. Although most of the identified gene mutations present a monogenic inheritance, most of idiopathic epilepsies are complex genetic diseases exhibiting a polygenic or oligogenic inheritance. This article reviews recent genetic and molecular progresses in exploring the pathogenesis of epilepsy, with special emphasis on monogenic epilepsy-causing genes, including voltage-gated channels (Na(+), K(+), Ca(2+), Cl(-), and HCN), ligand-gated channels (nicotinic acetylcholine and GABAA receptors), non-ion channel genes as well as the mitochondrial DNA genes. These progresses have improved our understanding of the complex neurological disorder.
    Molecular Neurobiology 08/2013; 49(1). DOI:10.1007/s12035-013-8523-6 · 5.14 Impact Factor
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    ABSTRACT: Wilson's disease (WD) is an autosomal recessive inherited disorder caused by mutations in the ATPase Cu(2+) transporting beta polypeptide gene (ATP7B). The detailed metabolism of copper-induced pathology in WD is still unknown. Gene mutations as well as the possible pathways involved in the ATP7B deficiency were documented. The ATP7B gene was analyzed for mutations in 18 Chinese Han families with WD by direct sequencing. Cell viability and apoptosis analysis of ATP7B small interfering RNA (siRNA)-treated human liver carcinoma (HepG2) cells were measured by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay and Hoechst 33342 staining. Finally, the expression of B-cell CLL/lymphoma 2 (BCL2), BCL2-associated X protein (BAX), sterol regulatory element binding protein 1 (SREBP1), and minichromosome maintenance protein 7 (MCM7) of ATP7B siRNA-treated cells were tested by real-time polymerase chain reaction (real-time PCR) and Western blot analysis. Twenty different mutations including four novel mutations (p.Val145Phe, p.Glu388X, p.Thr498Ser and p.Gly837X) in the ATP7B gene were identified in our families. Haplotype analysis revealed that founder effects for four mutations (p.Arg778Leu, p.Pro992Leu, p.Ile1148Thr and p.Ala1295Val) existed in these families. Transfection of HepG2 cells with ATP7B siRNA resulted in decreased mRNA expression by 86.3%, 93.1% and 90.8%, and decreased protein levels by 58.5%, 85.5% and 82.1% at 24, 48 and 72 hours, respectively (All P<0.01). In vitro study revealed that the apoptotic, cell cycle and lipid metabolism pathway may be involved in the mechanism of WD. Our results revealed that the genetic cause of 18 Chinese families with WD and ATP7B deficiency-induce apoptosis may result from imbalance in cell cycle and lipid metabolism pathway.
    PLoS ONE 07/2013; 8(7):e66526. DOI:10.1371/journal.pone.0066526 · 3.23 Impact Factor

Publication Stats

147 Citations
108.55 Total Impact Points


  • 2009–2015
    • The Third Xiangya Hospital of the Central South University
      Ch’ang-sha-shih, Hunan, China
  • 2013–2014
    • South Central College
      Central, Louisiana, United States
  • 2010–2013
    • Central South University
      • • Department of Neurology
      • • Center of Experimental Medicine
      Ch’ang-sha-shih, Hunan, China
  • 2012
    • Xiangya Hospital of Central South University
      Ch’ang-sha-shih, Hunan, China