ZIC1 Function in Normal Cerebellar Development and Human Developmental Pathology

Aruga, Jun; Millen, Kathleen J.

doi:10.1007/978-981-10-7311-3_13

Cited by 38 publications

(25 citation statements)

References 56 publications

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“…The DMR overlapping ZIC1 and ZIC4 was hypermethylated (by 2.5 percentage points) in WS and gained methylation with age (0.14 percentage points per year). The transcription factors ZIC1 and ZIC4 are involved in brain development (Aruga & Millen, ) and may also have a role in bone cells. The promoter DMR in the protein phosphatase 1 regulatory subunit 18 ( PPP1R18 ) was hypomethylated (by −4 and −6 percentage points, respectively) in WRN ‐ and POLD1 ‐mutant patients and lost methylation with age (−0.11 percentage points per year).…”

Section: Discussionmentioning

confidence: 99%

Epigenetic signatures of Werner syndrome occur early in life and are distinct from normal epigenetic aging processes

Maierhofer¹,

Flunkert²,

Oshima

et al. 2019

Aging Cell

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Werner Syndrome (WS) is an adult‐onset segmental progeroid syndrome. Bisulfite pyrosequencing of repetitive DNA families revealed comparable blood DNA methylation levels between classical (18 WRN‐mutant) or atypical WS (3 LMNA‐mutant and 3 POLD1‐mutant) patients and age‐ and sex‐matched controls. WS was not associated with either age‐related accelerated global losses of ALU, LINE1, and α‐satellite DNA methylations or gains of rDNA methylation. Single CpG methylation was analyzed with Infinium MethylationEPIC arrays. In a correspondence analysis, atypical WS samples clustered together with the controls and were clearly separated from classical WS, consistent with distinct epigenetic pathologies. In classical WS, we identified 659 differentially methylated regions (DMRs) comprising 3,656 CpG sites and 613 RefSeq genes. The top DMR was located in the HOXA4 promoter. Additional DMR genes included LMNA, POLD1, and 132 genes which have been reported to be differentially expressed in WRN‐mutant/depleted cells. DMRs were enriched in genes with molecular functions linked to transcription factor activity and sequence‐specific DNA binding to promoters transcribed by RNA polymerase II. We propose that transcriptional misregulation of downstream genes by the absence of WRN protein contributes to the variable premature aging phenotypes of WS. There were no CpG sites showing significant differences in DNA methylation changes with age between WS patients and controls. Genes with both WS‐ and age‐related methylation changes exhibited a constant offset of methylation between WRN‐mutant patients and controls across the entire analyzed age range. WS‐specific epigenetic signatures occur early in life and do not simply reflect an acceleration of normal epigenetic aging processes.

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Section: Discussionmentioning

confidence: 99%

Epigenetic signatures of Werner syndrome occur early in life and are distinct from normal epigenetic aging processes

Maierhofer¹,

Flunkert²,

Oshima

et al. 2019

Aging Cell

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show abstract

“…Of these, Plscr4, Armc8, Zbtb38, Rbp1, Zic1, and Trpc1 have been linked to schizophrenia or schizophrenia-related disorders in previous studies (Kim et al, 2007;Li et al, 2017). For example, Zic genes are strongly expressed in the cerebellum and have been shown to mediate cerebellar development (Aruga and Millen, 2018), and behavioral abnormalities of Zic1 mutant mice can serve as models for diseases involving sensorimotor gating abnormalities, such as schizophrenia (Ogura et al, 2001).…”

Section: Mouse Gene Expressionmentioning

confidence: 99%

A Cross-Species Systems Genetics Analysis Links APBB1IP as a Candidate for Schizophrenia and Prepulse Inhibition

Ashbrook

Cahill

Hager

2019

Front. Behav. Neurosci.

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“…DW malformation may be associated with poor intellectual outcome particularly when other cerebral anomalies are present [17][18][19]. DW malformation has been reported to have an heterogeneous aetiology, including mutations in genes of fibroblast growth factors and in genes in the sonic hedgehog (Shh) signalling pathway [20][21][22]. Many studies report associations with chromosomal anomalies and genetic syndromes [4,14,23,24].…”

Section: Introductionmentioning

confidence: 99%

Epidemiology of Dandy-Walker Malformation in Europe: A EUROCAT Population-Based Registry Study

et al. 2019

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Background: Dandy-Walker (DW) malformation is a rare and severe congenital anomaly of the posterior fossa affecting the development of the cerebellum and the fourth ventricle. Objective: The aim of this study was to investigate the epidemiology of DW malformation, using data from the European population-based registries of congenital anomalies in the European Surveillance of Congenital Anomalies network. Methods: Anonymous individual data on cases of DW malformation diagnosed in 2002–2015 from 28 registries in 17 countries were included. Prevalence, prenatal detection rate, proportions and types of associated anomalies were estimated. Cases of DW variant were considered and analysed separately. Results: Out of 8,028,454 surveyed births we identified a total of 734 cases, including 562 DW malformation cases and 172 DW variant cases. The overall prevalence of DW malformation was 6.79 per 100,000 births (95% CI 5.79–7.96) with 39.2% livebirths, 4.3% foetal deaths from 20 weeks gestational age, and 56.5% terminations of pregnancy after prenatal diagnosis of foetal anomaly at any gestation (TOPFA). The livebirth prevalence was 2.74 per 100,000 births (95% CI 2.08–3.61). The prenatal detection rate was 87.6%. Two-hundred and seventy-three cases (48.6%) had an isolated cerebral anomaly and 24.2, 19.2 and 5.5% cases were associated with other structural non-cerebral anomalies, chromosomal anomalies and genetic syndromes respectively. The prevalence of DW variant was 2.08 per 100,000 (95% CI 1.39–3.13). Conclusions: This European population-based study provides the epidemiological profile of DW malformation. All birth outcomes were analysed and TOPFA represented more than half of the cases. About 50% of the cases of DW malformation were associated with other non-cerebral anomalies. Large populations and all birth outcomes are essential in epidemiological studies of rare and severe congenital anomalies.

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ZIC1 Function in Normal Cerebellar Development and Human Developmental Pathology

Cited by 38 publications

References 56 publications

Epigenetic signatures of Werner syndrome occur early in life and are distinct from normal epigenetic aging processes

Epigenetic signatures of Werner syndrome occur early in life and are distinct from normal epigenetic aging processes

A Cross-Species Systems Genetics Analysis Links APBB1IP as a Candidate for Schizophrenia and Prepulse Inhibition

Epidemiology of Dandy-Walker Malformation in Europe: A EUROCAT Population-Based Registry Study

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