Analysis of mitochondrial DNA variations in a Chinese family with spinocerebellar ataxia

Zeng, Aiping; Li, Xinwei; Shen, Lijun; Li, Weizhen; Ding, Zhongying; Bai, Yidong; Lü, Jianxin

doi:10.1016/j.jocn.2011.05.011

Cited by 6 publications

(4 citation statements)

References 28 publications

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“…Regulation of cellular proliferation occurs at two distinct cell cycle transitions: the G1 to S phase and the S to G2 phase. As cellular proliferation is initiated at the S phase, DNA content of the various cell cycle phases was assayed by flow cytometric analysis to investigate the effect of BDV infection on cellular proliferation; the PI was used as an indicator of cell proliferation [26]. From 0 h post-serum release, the Strain V cells showed a higher PI than the control cells (Table 2, Figure 4).…”

Section: Discussionmentioning

confidence: 99%

Human but Not Laboratory Borna Disease Virus Inhibits Proliferation and Induces Apoptosis in Human Oligodendrocytes In Vitro

Yang

Deng

et al. 2013

PLoS ONE

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Borna disease virus (BDV) is a neurotropic virus that produces neuropsychiatric dysfunction in a wide range of warm-blooded species. Several studies have associated BDV with human psychiatric illness, but the findings remain controversial. Although oligodendrocytes are a major glial component of brain white matter and play a pivotal role in neuronal cell function, BDV's effects on human oligodendrocytes have not been clarified. Here, the effects of two BDV strains, Hu-H1 (isolated from a bipolar patient) and Strain V (a laboratory strain), on the proliferation and apoptosis of human oligodendrocytes were investigated. Three experimental cell lines were constructed: Hu-H1-infected oligodendroglioma (Hu-H1) cells, Strain V-infected oligodendroglioma (Strain V) cells, and non-infected oligodendroglioma (control) cells. BDV infection was assayed by BDV nucleoprotein (p40) immunofluorescence, cell proliferation was assayed by Cell Counting Kit-8 (CCK8), and cell cycle phases and apoptosis were assayed by flow cytometry. Expressions of the apoptosis-related proteins Bax and Bcl-2 were measured by Western blotting. p40 expression was confirmed in Hu-H1 and Strain V on and after day three post-infection. Strain V cells showed significantly greater cellular proliferation than Hu-H1 cells on and after day three post-infection. In Hu-H1 cells, Bax and Bcl-2 expression were significantly increased and decreased, respectively, on and after day three post-infection. In contrast, in Strain V cells, Bax and Bcl-2 expression were significantly decreased and increased, respectively, on and after day three post-infection. In conclusion, Hu-H1 inhibits cellular proliferation and promotes apoptosis in human oligodendrocytes via Bax upregulation and Bcl-2 downregulation. In contrast, Strain V promotes cellular proliferation and inhibits apoptosis in human oligodendrocytes via Bax downregulation and Bcl-2 upregulation. The effects of the Hu-H1 strain (isolated from a bipolar patient) are opposite from those of Strain V (a laboratory strain), thereby providing a proof of authenticity for both.

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Section: Discussionmentioning

confidence: 99%

Human but Not Laboratory Borna Disease Virus Inhibits Proliferation and Induces Apoptosis in Human Oligodendrocytes In Vitro

Yang

Deng

et al. 2013

PLoS ONE

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“…Yu and colleagues also observed lower mtDNA copy number as well as lower levels of del4977 in 16 MJD patients compared to controls [1]. In a later study, similar levels of mtDNA copy number and del4977, without controlling age at sampling, were found in MJD patients [4]. Power limitations as well as the non-adjustment of age at sampling as covariate could be the cause of the inconclusive findings.…”

Section: Introductionmentioning

confidence: 91%

“…Mitochondrial DNA (mtDNA) depletion and an increased number of large deletions, namely the common deletion (m.8482_13460del4977, hereafter named as del4977), previously associated with neurodegeneration, have been observed in Machado-Joseph disease (MJD) cell lines and transgenic (TG) animal models [1][2][3], as well as in blood samples from MJD patients [1,4,5]. MJD, also known as spinocerebellar ataxia type 3 (SCA3; MIM#109150; ORPHA98757), is an autosomal dominant late-onset proteinopathy, which is caused by an abnormal number of coding CAG repeats in the gene encoding for ataxin-3 -ATXN3 (reviewed in [6]).…”

Section: Introductionmentioning

confidence: 99%

Accumulation of Mitochondrial DNA Common Deletion Since The Preataxic Stage of Machado-Joseph Disease

et al. 2018

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Molecular alterations reflecting pathophysiologic changes thought to occur many years before the clinical onset of Machado-Joseph disease (MJD)/spinocerebellar ataxia type 3 (SCA3), a late-onset polyglutamine disorder, remain unidentified. The absence of molecular biomarkers hampers clinical trials, which lack sensitive measures of disease progression, preventing the identification of events occurring prior to clinical onset. Our aim was to analyse the mtDNA content and the amount of the common deletion (m.8482_13460del4977) in a cohort of 16 preataxic MJD mutation carriers, 85 MJD patients and 101 apparently healthy age-matched controls. Relative expression levels of RPPH1, MT-ND1 and MT-ND4 genes were assessed by quantitative real-time PCR. The mtDNA content was calculated as the difference between the expression levels of a mitochondrial gene (MT-ND1) and a nuclear gene (RPPH1); the amount of mtDNA common deletion was calculated as the difference between expression levels of a deleted (MT-ND4) and an undeleted (MT-ND1) mitochondrial genes. mtDNA content in MJD carriers was similar to that of healthy age-matched controls, whereas the percentage of the common deletion was significantly increased in MJD subjects, and more pronounced in the preclinical stage (p < 0.05). The BCL2/BAX ratio was decreased in preataxic carriers compared to controls, suggesting that the mitochondrial-mediated apoptotic pathway is altered in MJD. Our findings demonstrate for the first time that accumulation of common deletion starts in the preclinical stage. Such early alterations provide support to the current understanding that any therapeutic intervention in MJD should start before the overt clinical phenotype.

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“…Accordingly to the already published method [17], all samples have been run by sequencer DNA analyser ABI 3031 (microsatellite analysis) and analysed by the Gene Mapper software.…”

Section: Methodsmentioning

confidence: 99%

New CACNA1A deletions are associated to migraine phenotypes

et al. 2018

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BackgroundFamilial hemiplegic migraine type 1 (FHM1) is a form of migraine with aura caused by heterozygous mutations in 4 genes: CACNA1A, ATP1A2, SNC1A and PRRT2, but further heterogeneity is expected. Here have been described clinical and molecular features in patients suffering from migraine with Aura (MA), without (MO) and hemiplegic migraine attacks.Next Generation Sequencing by TruSeq Custom Amplicon for CACNA1A and ATP1A2 gene has been performed. All genetic variants have been confirmed by Sanger sequencing and all samples were also analyzed with MLPA assay for ATP1A2-CACNA1A genes to detect duplication or deletion. All MLPA data were verified by Real Time PCR.ResultsSequencing analysis showed 3 point mutations, two novel variants and one already described in literature. Moreover, MLPA analysis showed 3 deletions in 9 sporadic hemiplegic migraine (18%), in 3 patients with non-hemiplegic migraine (4.1%) and in 3 patients affected by episodic ataxia (20%). Two sporadic patients showed a deletion in exons 41–43, while the rest of HM patients (5) showed a deletion in the terminal part of the CACNA1A gene.About episodic ataxia, we have identified deletions in exon 12–15 and in exon 47. Finally, in migraine patients, we have found different subjects affected by different phenotypes deleted in exon 47.ConclusionThis work highlights the importance to complement analysis as direct sequencing with quantitative analysis (MLPA). In fact, intragenic CACNA1A rearrangements have been detected. Our work demonstrated that deletions in CACNA1A gene may be associated also to different migraine phenotypes.

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Analysis of mitochondrial DNA variations in a Chinese family with spinocerebellar ataxia

Cited by 6 publications

References 28 publications

Human but Not Laboratory Borna Disease Virus Inhibits Proliferation and Induces Apoptosis in Human Oligodendrocytes In Vitro

Human but Not Laboratory Borna Disease Virus Inhibits Proliferation and Induces Apoptosis in Human Oligodendrocytes In Vitro

Accumulation of Mitochondrial DNA Common Deletion Since The Preataxic Stage of Machado-Joseph Disease

New CACNA1A deletions are associated to migraine phenotypes

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