Temple syndrome and Kagami-Ogata syndrome: clinical presentations, genotypes, models and mechanisms

Prasasya, Rexxi D.; Grotheer, Kristen V; Siracusa, Linda D.; Bartolomei, Marisa S.

doi:10.1093/hmg/ddaa133

Cited by 38 publications

(47 citation statements)

References 82 publications

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“…Generally, individuals with maternal deletions in this region lack expression of the maternally expressed genes, but show overexpression of DLK1 in blood and placenta (Ogata and Kagami 2016). In Temple syndrome, DLK1 expression is lost due to the paternal deletion of this locus (Prasasya et al 2020). We found evidence for imprinting of DLK1 gene expression in progenitors but not neurons (Figure 5C and 5D; Supplemental Figure 2E).…”

Section: Imprinted Res and Genes Indicate Isoform-specific Imprinting In Neuronsmentioning

confidence: 74%

Inference of cell-type specific imprinted regulatory elements and genes during human neuronal differentiation

Liang

Aygün

Matoba

et al. 2021

Preprint

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Genomic imprinting results in gene expression biased by parental chromosome of origin and occurs in genes with important roles during human brain development. However, the cell-type and temporal specificity of imprinting during human neurogenesis is generally unknown. By detecting within-donor allelic biases in chromatin accessibility and gene expression that are unrelated to cross-donor genotype, we inferred imprinting in both primary human neural progenitor cells (phNPCs) and their differentiated neuronal progeny from up to 85 donors. We identified 43/20 putatively imprinted regulatory elements (IREs) in neurons/progenitors, and 133/79 putatively imprinted genes in neurons/progenitors. Though 10 IREs and 42 genes were shared between neurons and progenitors, most imprinting was only detected within specific cell types. In addition to well-known imprinted genes and their promoters, we inferred novel IREs and imprinted genes. We found IREs overlapped with CpG islands more than non-imprinted regulatory elements. Consistent with DNA methylation-based regulation of imprinted expression, some putatively imprinted regulatory elements also overlapped with differentially methylated regions on the maternal germline. Finally, we identified a progenitor-specific putatively imprinted gene overlap with copy number variation that is associated with uniparental disomy-like phenotypes. Our results can therefore be useful in interpreting the function of variants identified in future parent-of-origin association studies.

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Section: Imprinted Res and Genes Indicate Isoform-specific Imprinting In Neuronsmentioning

confidence: 74%

Inference of cell-type specific imprinted regulatory elements and genes during human neuronal differentiation

Liang

Aygün

Matoba

et al. 2021

Preprint

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“…Animal models are also advantageous for investigations into the underlying mechanisms of IDs. Mouse models of several IDs, including those associated with ART, have been developed, including BWS, SRS, PWS, AS and KOS, and Temple syndromes [37][38][39][40][41].…”

Section: Mouse Models For Imprinting and Artmentioning

confidence: 99%

Epigenetic Mechanisms of ART-Related Imprinting Disorders: Lessons From iPSC and Mouse Models

Horánszky

Becker

Zana

et al. 2021

Genes

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The rising frequency of ART-conceived births is accompanied by the need for an improved understanding of the implications of ART on gametes and embryos. Increasing evidence from mouse models and human epidemiological data suggests that ART procedures may play a role in the pathophysiology of certain imprinting disorders (IDs), including Beckwith-Wiedemann syndrome, Silver-Russell syndrome, Prader-Willi syndrome, and Angelman syndrome. The underlying molecular basis of this association, however, requires further elucidation. In this review, we discuss the epigenetic and imprinting alterations of in vivo mouse models and human iPSC models of ART. Mouse models have demonstrated aberrant regulation of imprinted genes involved with ART-related IDs. In the past decade, iPSC technology has provided a platform for patient-specific cellular models of culture-associated perturbed imprinting. However, despite ongoing efforts, a deeper understanding of the susceptibility of iPSCs to epigenetic perturbation is required if they are to be reliably used for modelling ART-associated IDs. Comparing the patterns of susceptibility of imprinted genes in mouse models and IPSCs in culture improves the current understanding of the underlying mechanisms of ART-linked IDs with implications for our understanding of the influence of environmental factors such as culture and hormone treatments on epigenetically important regions of the genome such as imprints.

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“…Genetic and epigenetic alterations in delta-like homolog 1 gene/type III iodothyronine deiodinase gene ( DLK1/DIO3 ) imprinted cluster on human chromosome 14q32 are associated with two human imprinting disorder-related diseases, KOS14 and TS14 ( Temple et al, 1991 ; Wang et al, 1991 ; Ogata and Kagami, 2016 ). Common KOS14 phenotypes include neonatal respiratory difficulties, a distinctive facial appearance, variable developmental delay, and/or intellectual disability ( Ogata and Kagami, 2016 ; Prasasya et al, 2020 ). Clinical syndromes observed in TS14 include severe intrauterine growth restriction, postnatal growth restriction, neonatal hypotonia, and feeding difficulties in infancy ( Ioannides et al, 2014 ; Gillessen-Kaesbach et al, 2018 ; Prasasya et al, 2020 ).…”

Section: The Role Of Imprinted Long Non-coding Rnas In Human Imprinting Disorders and Cancermentioning

confidence: 99%

The Role of Long Non-coding RNAs in Human Imprinting Disorders: Prospective Therapeutic Targets

Wang

Jianjian

Yang

et al. 2021

Front. Cell Dev. Biol.

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Genomic imprinting is a term used for an intergenerational epigenetic inheritance and involves a subset of genes expressed in a parent-of-origin-dependent way. Imprinted genes are expressed preferentially from either the paternally or maternally inherited allele. Long non-coding RNAs play essential roles in regulating this allele-specific expression. In several well-studied imprinting clusters, long non-coding RNAs have been found to be essential in regulating temporal- and spatial-specific establishment and maintenance of imprinting patterns. Furthermore, recent insights into the epigenetic pathological mechanisms underlying human genomic imprinting disorders suggest that allele-specific expressed imprinted long non-coding RNAs serve as an upstream regulator of the expression of other protein-coding or non-coding imprinted genes in the same cluster. Aberrantly expressed long non-coding RNAs result in bi-allelic expression or silencing of neighboring imprinted genes. Here, we review the emerging roles of long non-coding RNAs in regulating the expression of imprinted genes, especially in human imprinting disorders, and discuss three strategies targeting the central long non-coding RNA UBE3A-ATS for the purpose of developing therapies for the imprinting disorders Prader–Willi syndrome and Angelman syndrome. In summary, a better understanding of long non-coding RNA-related mechanisms is key to the development of potential therapeutic targets for human imprinting disorders.

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Temple syndrome and Kagami-Ogata syndrome: clinical presentations, genotypes, models and mechanisms

Cited by 38 publications

References 82 publications

Inference of cell-type specific imprinted regulatory elements and genes during human neuronal differentiation

Inference of cell-type specific imprinted regulatory elements and genes during human neuronal differentiation

Epigenetic Mechanisms of ART-Related Imprinting Disorders: Lessons From iPSC and Mouse Models

The Role of Long Non-coding RNAs in Human Imprinting Disorders: Prospective Therapeutic Targets

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