Clinical and Molecular Diagnosis of Beckwith-Wiedemann Syndrome with Single- or Multi-Locus Imprinting Disturbance

Fontana, Laura; Tabano, Silvia; Maitz, Silvia; Colapietro, Patrizia; Garzia, Emanuele; Gerli, Alberto Giovanni; Sirchia, Silvia Maria; Miozzo, Monica

doi:10.3390/ijms22073445

Cited by 23 publications

(29 citation statements)

References 101 publications

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“…These eight MEGs are all involved in methylation and imprinting. A role for methylation and imprinting abnormalities in the etiology of structural birth defects is consistent with the occurrence of such conditions in imprinting syndromes (e.g., omphalocele in Beckwith-Wiedemann syndrome) 83 , 93 and has been suggested based on studies of non-syndromic structural birth defects. 94 , 95 , 96 , 97 Further, epigenetic and imprinting differences resulting from ARTs have been suggested as a potential cause for the increased risk of structural birth defects in offspring conceived by in vitro fertilization or intracytoplasmic sperm injection.…”

Section: Discussionsupporting

confidence: 54%

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Maternal effect genes: Update and review of evidence for a link with birth defects

Mitchell

2022

Human Genetics and Genomics Advances

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Summary Maternal effect genes (MEGs) encode factors (e.g., RNA) that are present in the oocyte and required for early embryonic development. Hence, while these genes and gene products are of maternal origin, their phenotypic consequences result from effects on the embryo. The first mammalian MEGs were identified in the mouse in 2000 and were associated with early embryonic loss in the offspring of homozygous null females. In humans, the first MEG was identified in 2006, in women who had experienced a range of adverse reproductive outcomes, including hydatidiform moles, spontaneous abortions, and stillbirths. Over 80 mammalian MEGs have subsequently been identified, including several that have been associated with phenotypes in humans. In general, pathogenic variants in MEGs or the absence of MEG products are associated with a spectrum of adverse outcomes, which in humans range from zygotic cleavage failure to offspring with multi-locus imprinting disorders. Although less established, there is also evidence that MEGs are associated with structural birth defects (e.g., craniofacial malformations, congenital heart defects). This review provides an updated summary of mammalian MEGs reported in the literature through early 2021, as well as an overview of the evidence for a link between MEGs and structural birth defects.

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Section: Discussionsupporting

confidence: 54%

“…While omphalocele is common feature of the Beckwith-Wiedemann syndrome, heart defects are not considered to be either major or minor clinical features of this syndrome. 83 …”

Section: Updated List Of Mammalian Megsmentioning

confidence: 99%

Maternal effect genes: Update and review of evidence for a link with birth defects

Mitchell

2022

Human Genetics and Genomics Advances

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“…They share a common imprinting mechanism and are downregulated in many human cancers and fetal growth syndromes. A study found that when the methylation defect occurred in this region, it led to Beckwith–Wiedemann syndrome (BWS) (Fontana et al 2021 ). The combination of H19 and S-adenosylhomocysteine hydrolase (SAHH) can interfere with the hydrolysis ability of S-adenosylhomocysteine (SAH), and SAH is an effective product inhibitor of adenylate-dependent methyltransferase.…”

Section: Discussionmentioning

confidence: 99%

Role of long non-coding RNA H19 in the development of osteoporosis

Chen

Liu

Zhou

et al. 2021

Mol Med

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Background Osteoporosis is a widespread and serious metabolic bone disease. At present, revealing the molecular mechanisms of osteoporosis and developing effective prevention and treatment methods are of great significance to health worldwide. LncRNA is a non-coding RNA peptide chain with more than 200 nucleotides. Researchers have identified many lncRNAs implicated in the development of diseases and lncRNA H19 is an example. Results A large amount of evidence supports the fact that long non-coding RNA (lncRNA) genes, such as H19, have multiple, far-reaching effects on various biological functions. It has been found that lncRNA H19 has a role in the regulation of different types of cells in the body including the osteoblasts, osteocytes, and osteoclasts found in bones. Therefore, it can be postulated that lncRNA H19 affects the incidence and development of osteoporosis. Conclusion The prospect of targeting lncRNA H19 in the treatment of osteoporosis is promising because of the effects that lncRNA H19 has on the process of osteogenic differentiation. In this review, we summarize the molecular pathways and mechanisms of lncRNA H19 in the pathogenesis of osteoporosis and summarize the research progress of targeting H19 as a treatment option. Research is emerging that explores more effective treatment possibilities for bone metabolism diseases using molecular targets.

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“…Imprinting disorders are frequently associated with growth and development abnormalities [ 54 , 55 ]; similarly, prenatal and postnatal growth restriction are observed in CdLS patients [ 56 ]. This feature might be also related to an imprinting network perturbation suggested by our data.…”

Section: Discussionmentioning

confidence: 99%

“…This feature might be also related to an imprinting network perturbation suggested by our data. In particular, we found methylation instability of the DMRs and/or defective expression of loci involved in fetal growth such as PEG10 , MEST , GNAS , IGF2 and H19 [ 55 , 56 , 57 ].…”

Section: Discussionmentioning

confidence: 99%

Cohesin Mutations Induce Chromatin Conformation Perturbation of the H19/IGF2 Imprinted Region and Gene Expression Dysregulation in Cornelia de Lange Syndrome Cell Lines

et al. 2021

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Traditionally, Cornelia de Lange Syndrome (CdLS) is considered a cohesinopathy caused by constitutive mutations in cohesin complex genes. Cohesin is a major regulator of chromatin architecture, including the formation of chromatin loops at the imprinted IGF2/H19 domain. We used 3C analysis on lymphoblastoid cells from CdLS patients carrying mutations in NIPBL and SMC1A genes to explore 3D chromatin structure of the IGF2/H19 locus and evaluate the influence of cohesin alterations in chromatin architecture. We also assessed quantitative expression of imprinted loci and WNT pathway genes, together with DMR methylation status of the imprinted genes. A general impairment of chromatin architecture and the emergence of new interactions were found. Moreover, imprinting alterations also involved the expression and methylation levels of imprinted genes, suggesting an association among cohesin genetic defects, chromatin architecture impairment, and imprinting network alteration. The WNT pathway resulted dysregulated: canonical WNT, cell cycle, and WNT signal negative regulation were the most significantly affected subpathways. Among the deregulated pathway nodes, the key node of the frizzled receptors was repressed. Our study provides new evidence that mutations in genes of the cohesin complex have effects on the chromatin architecture and epigenetic stability of genes commonly regulated by high order chromatin structure.

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Clinical and Molecular Diagnosis of Beckwith-Wiedemann Syndrome with Single- or Multi-Locus Imprinting Disturbance

Cited by 23 publications

References 101 publications

Maternal effect genes: Update and review of evidence for a link with birth defects

Maternal effect genes: Update and review of evidence for a link with birth defects

Role of long non-coding RNA H19 in the development of osteoporosis

Cohesin Mutations Induce Chromatin Conformation Perturbation of the H19/IGF2 Imprinted Region and Gene Expression Dysregulation in Cornelia de Lange Syndrome Cell Lines

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