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Loss-of-function maternal-effect mutations of PADI6 are associated with familial and sporadic Beckwith-Wiedemann Syndrome with multi-locus imprinting disturbance

ABSTRACT: PADI6 is a component of the subcortical maternal complex (SCMC) which is a group of proteins that are abundantly expressed in the oocyte cytoplasm and essential for the proper development of the early embryo. The mutation(s) in the components of the subcortical maternal complex have been associated with reproductive failures, including formation of hydatidiform mole, female infertility and imprinting disorders with multi-locus imprinting disturbance (MLIDs).In the current study by using whole-exome sequencing analysis, we identified four cases of Beckwith-Wiedemann Syndrome with multi-locus imprinting disturbance while their mothers were carriers of variants in PADI6 gene. Genome-wide methylation profiling using Methylation EPIC array depicted the loss of methylation specifically at several known imprinted loci in affected individuals as compared to healthy siblings, parents and controls. Our findings firmly establish the role of PADI6 in imprinting disorders.

ORGANISM(S): Homo sapiens

PROVIDER: GSE153211 | GEO | 2020/10/02

REPOSITORIES: GEO

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A maternal-effect Padi6 variant causes nuclear and cytoplasmic abnormalities in oocytes as well as failure of epigenetic reprogramming and zygotic genome activation in embryos [WGS]

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| PRJNA641739 | ENA

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