Corrigendum. Imprinting disorders in children born after ART: a Nordic study from the CoNARTaS group

This chapter provides a thorough overview of Beckwith-Wiedemann syndrome, which is considered to be the most common of the overgrowth syndromes and imprinting disorders. It starts with a description of the clinical aspects of the condition, including diagnostic criteria, differential diagnosis, risk of malignancy, and management. This is followed by an in-depth description of the genetic causes of the syndrome and of the molecular pathways involved in the pathogenesis of this disorder. The complexities of the etiology, which involves two neighboring loci, each one regulated by finely tuned imprinting mechanisms, are clearly delineated. The chapter also touches on the reported association between in vitro fertilization and risk of conceiving a baby with this syndrome.

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In Pursuit of New Imprinting Syndromes by Epimutation Screening in Idiopathic Neurodevelopmental Disorder Patients

BioMed Research International ◽

10.1155/2015/341986 ◽

2015 ◽

Vol 2015 ◽

pp. 1-8 ◽

Cited By ~ 2

Author(s):

Sonia Mayo ◽

Sandra Monfort ◽

Mónica Roselló ◽

Silvestre Oltra ◽

Carmen Orellana ◽

...

Keyword(s):

Clinical Features ◽

Neurodevelopmental Disorders ◽

Neurodevelopmental Disorder ◽

Epigenetic Mechanisms ◽

Proof Of Concept ◽

Partial Loss ◽

Imprinting Disorders ◽

Initial Hypothesis ◽

Definition Of ◽

Methylation Patterns

Alterations of epigenetic mechanisms, and more specifically imprinting modifications, could be responsible of neurodevelopmental disorders such as intellectual disability (ID) or autism together with other associated clinical features in many cases. Currently only eight imprinting syndromes are defined in spite of the fact that more than 200 genes are known or predicted to be imprinted. Recent publications point out that some epimutations which cause imprinting disorders may affect simultaneously different imprintedloci, suggesting that DNA-methylation may have been altered more globally. Therefore, we hypothesised that the detection of altered methylation patterns in known imprintinglociwill indirectly allow identifying new syndromes due to epimutations among patients with unexplained ID. In a screening for imprinting alterations in 412 patients with syndromic ID/autism we found five patients with altered methylation in the four genes studied:MEG3, H19, KCNQ1OT1, andSNRPN. Remarkably, the cases with partial loss of methylation inKCNQ1OT1andSNRPNpresent clinical features different to those associated with the corresponding imprinting syndromes, suggesting a multilocus methylation defect in accordance with our initial hypothesis. Consequently, our results are a proof of concept that the identification of epimutations in knownlociin patients with clinical features different from those associated with known syndromes will eventually lead to the definition of new imprinting disorders.

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Imprinting disorders and assisted reproductive technology

Fertility and Sterility ◽

10.1016/j.fertnstert.2009.01.002 ◽

2009 ◽

Vol 91 (2) ◽

pp. 305-315 ◽

Cited By ~ 215

Author(s):

Somjate Manipalviratn ◽

Alan DeCherney ◽

James Segars

Keyword(s):

Assisted Reproductive Technology ◽

Reproductive Technology ◽

Imprinting Disorders

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The phenotypic variations of multi-locus imprinting disturbances associated with maternal-effect variants of NLRP5 range from overt imprinting disorder to apparently healthy phenotype

Clinical Epigenetics ◽

10.1186/s13148-019-0760-8 ◽

2019 ◽

Vol 11 (1) ◽

Cited By ~ 5

Author(s):

Angela Sparago ◽

Ankit Verma ◽

Maria Grazia Patricelli ◽

Laura Pignata ◽

Silvia Russo ◽

...

Keyword(s):

Maternal Effect ◽

Multiple Pregnancy ◽

Principal Component ◽

Loss Of Function ◽

Imprinting Disorders ◽

Imprinting Disorder ◽

Whole Exome ◽

Genome Analyses ◽

Methylation Patterns ◽

And Control

Abstract Background A subset of individuals affected by imprinting disorders displays multi-locus imprinting disturbances (MLID). MLID has been associated with maternal-effect variants that alter the maintenance of methylation at germline-derived differentially methylated regions (gDMRs) in early embryogenesis. Pedigrees of individuals with MLID also include siblings with healthy phenotype. However, it is unknown if these healthy individuals have MLID themselves or if their methylation patterns differ from those associated with imprinting disorders, and in general, if MLID affects the clinical phenotype. Methods We have investigated gDMR methylation by locus-specific and whole-genome analyses in a family with multiple pregnancy losses, a child with Beckwith-Wiedemann syndrome (BWS) and a further child with no clinical diagnosis of imprinting disorder or other pathologies. Results We detected MLID with different methylation profiles in the BWS-affected and healthy siblings. Whole-exome sequencing demonstrated the presence of novel loss-of-function variants of NLRP5 in compound heterozygosity in the mother. The methylation profiles of the two siblings were compared with those of other cases with MLID and control groups by principal component analysis and unsupervised hierarchical clustering, but while their patterns were clearly separated from those of controls, we were unable to cluster those associated with specific clinical phenotypes among the MLID cases. Conclusion The identification of two novel maternal-effect variants of NLRP5 associated with poly-abortivity and MLID adds further evidence to the role of this gene in the maintenance of genomic imprinting in early embryos. Furthermore, our results demonstrate that within these pedigrees, MLID can also be present in the progeny with healthy phenotype, indicating that some sort of compensation occurs between altered imprinted loci in these individuals. The analysis of larger cohorts of patients with MLID is needed to formulate more accurate epigenotype-phenotype correlations.

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