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Clinical spectrum of multi-locus imprinting disturbances associated with maternal-effect variants range from overt Beckwith-Wiedemann syndrome to apparently healthy phenotype

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE133774 | GEO | 2019/10/01

REPOSITORIES: GEO

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MLID imprinting disorders

Project description:MLID imprinting disorders

| PRJNA817519 | ENA

Clinical spectrum of multi-locus imprinting disturbances associated with maternal-effect variants range from overt Beckwith-Wiedemann syndrome to apparently healthy phenotype

Project description:Clinical spectrum of multi-locus imprinting disturbances associated with maternal-effect variants range from overt Beckwith-Wiedemann syndrome to apparently healthy phenotype

| PRJNA552530 | ENA

DNA methylation analysis in multi-locus imprinting disturbances

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