Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA313921 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The aim of our study was to characterize the genotypic and phenotypic extent of multi-locus imprinting disturbances. Therefore, we analyzed the DNA methylation pattern of 37 individuals with different DNA methylation disturbances. Of these 37 individuals 17 were previously diagnosed with a multi-locus methylation disturbance (MLID) and the remaing 20 were diagnosed with a typical single locus imprinting disorder (SLID). We compared the DNA methylation of these 37 individuals to the DNA methylation of 38 evaluable individuals born small for gestational age. Our analysis revealed 21/37 individuals with a multi-locus methylation disturbances, characterzied by an aberrant DNA methylation in more than one imprintend gene region. Validation analyses were performed by bisulfite-pyrosequencing in the two imprinted gene regions ZDBF2 and FAM50B. Our analyses revealed each one patient previously diagnosed with Temple- and Angelman syndrome to have MLID. Furthermore, we showed that many of the aberrantly methylated imprinted gene regions in patients with MLID are not associated with the so far known typical imprinting disorders.
2016-12-31 | GSE78773 | GEO
Project description:Nlrp5 encodes a core component of the subcortical maternal complex (SCMC) a cytoplasmic protein structure unique to the mammalian oocyte and cleavage-stage embryo. NLRP5 mutations have been identified in patients presenting with early embryo arrest, recurrent molar pregnancies and imprinting disorders. It was previously shown that oocytes with mutations in the human SCMC gene KHDC3L had globally impaired methylation, suggesting a requirement for integrity of the SCMC in the establishment of DNA methylation. Here, we present a multi-omic analysis of an Nlrp5-null mouse model. We detect global misregulation of maternal proteins, including profound reduction in the essential de novo methylation factor DNMT3L, which could contribute to attenuated de novo methylation we observe. In contrast, the maintenance methyltransferase DNMT1 exhibits normal cytoplasmic localisation. This provides evidence for mechanisms leading to downstream misregulation of imprinted genes, which in turn, may result in imprinting syndromes, multi-locus imprinting disturbances (MLID) and hydatidiform moles.
2025-12-22 | PXD056859 | Pride
Project description:Nlrp5 encodes a core component of the subcortical maternal complex (SCMC) a cytoplasmic protein structure unique to the mammalian oocyte and cleavage-stage embryo. NLRP5 mutations have been identified in patients presenting with early embryo arrest, recurrent molar pregnancies and imprinting disorders. Correct patterning of DNA methylation over imprinted domains during oogenesis is necessary for faithful imprinting of genes. It was previously shown that oocytes with mutations in the human SCMC gene KHDC3L had globally impaired methylation, suggesting a role for the SCMC in the establishment of DNA methylation at imprinted regions. Here, we present a multi-omic analysis of an Nlrp5-null mouse model, which displays a global misregulation of maternal proteins in Nlrp5-null oocytes, likely underlying oocyte developmental incompetence. We also show that de novo DNA methylation is altered in Nlrp5-null oocytes, and that epigenetic modifiers such as DNMT3L are significantly reduced. This provides evidence for mechanisms leading to downstream misregulation of imprinted genes, which in turn, may result in imprinting syndromes, multi-locus imprinting disturbances (MLID), and hydatidiform moles.
2025-12-30 | GSE278124 | GEO
Project description:Nlrp5 encodes a core component of the subcortical maternal complex (SCMC) a cytoplasmic protein structure unique to the mammalian oocyte and cleavage-stage embryo. NLRP5 mutations have been identified in patients presenting with early embryo arrest, recurrent molar pregnancies and imprinting disorders. Correct patterning of DNA methylation over imprinted domains during oogenesis is necessary for faithful imprinting of genes. It was previously shown that oocytes with mutations in the human SCMC gene KHDC3L had globally impaired methylation, suggesting a role for the SCMC in the establishment of DNA methylation at imprinted regions. Here, we present a multi-omic analysis of an Nlrp5-null mouse model, which displays a global misregulation of maternal proteins in Nlrp5-null oocytes, likely underlying oocyte developmental incompetence. We also show that de novo DNA methylation is altered in Nlrp5-null oocytes, and that epigenetic modifiers such as DNMT3L are significantly reduced. This provides evidence for mechanisms leading to downstream misregulation of imprinted genes, which in turn, may result in imprinting syndromes, multi-locus imprinting disturbances (MLID), and hydatidiform moles.
2025-12-30 | GSE278123 | GEO
Project description:Phenotypic spectrum and extent of DNA methylation defects associated with multi-locus imprinting disturbances
| PRJNA314498 | ENA
Project description:Uncovering the phenotypic consequences of multi-locus imprinting disturbances using genome-wide methylation analysis in genomic imprinting disorders
| PRJNA995541 | ENA
Project description:Multi-locus imprinting Disturbances (MLID) are methylation defects affecting germline-derived Differentially Methylated Regions (gDMRs) and they have been associated with maternal-effect variants causing imprinting disorders in the offspring. In a family with multiple pregnancy losses, a child with Beckwith-Wiedemann syndrome (BWS) and a further child without any features of imprinting disorders, novel compound heterozygous variants in the NLRP5 gene of the mother were found. Locus-specific and whole-genome methylation analysis by using Infinium MethylationEPIC BeadChip (WG-317-1001, Illumina) revealed MLID with different methylation profiles in both the siblings. The proband and the normal sibling were found to cluster with other MLID cases as shown by principal component analysis and unsupervised hierarchical clustering and remain distinct from controls. However, we were unable to cluster MLID cases associated with specific clinical phenotypes. The identification of two novel maternal-effect variants of NLRP5 associated with poly-abortivity and MLID add further evidence to the role of NLRP5 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.
2019-10-01 | GSE133774 | GEO
Project description:The expression of imprinted genes, which depends on their gamete of origin, is regulated by DNA sequences characterized by differential methylation between the maternal and paternal alleles (also known as germline differentially methylated regions or gDMRs). A common molecular defect associated with Beckwith-Wiedemann syndrome (BWS), a condition linked to overgrowth and tumors, is the loss of methylation of the KCNQ1OT1-TSS gDMR located on chromosome 11p15.5 (also known as IC2 LoM). Approximately one-third of BWS patients with IC2 LoM exhibit multi-locus imprinting disturbances (MLID). While maternal-effect variants in proteins of the oocyte subcortical maternal complex (SCMC) have been linked to MLID, the underlying mechanisms and health impacts of this epigenetic disturbance remain unclear.
2025-09-30 | GSE297935 | GEO
Project description:Highly variable genomic methylation in the Beckwith-Wiedemann syndrome associated with Multi-Locus Imprinting Disturbances
| PRJNA1266905 | ENA
Project description:Multi-locus imprinting disturbances in a family harboring a ZFP57 truncation
| PRJNA629286 | ENA