ArticleClinical epigenetics2020
Loss-of-function maternal-effect mutations of PADI6 are associated with familial and sporadic Beckwith-Wiedemann syndrome with multi-locus imprinting disturbance.
Article in Clinical epigenetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
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Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 85 citations in OpenAlex.
- Role of the PADI family in inflammatory autoimmune diseases and cancers: A systematic review.Frontiers in immunology · 2023Pooled it
- Article
- Concordant epigenetic and discordant clinical PHP1B/iPPSD3 manifestations in two monozygotic adolescent twins.Clinical epigenetics · 2026Article
- Investigation of multilocus imprinting disturbance (MLID) in 101 Beckwith-Wiedemann spectrum patients.Clinical epigenetics · 2026Article
- Loss of maternal PADI6 disrupts DNA methylation and genomic imprinting maintenance in late preimplantation mouse embryos.Epigenetics & chromatin · 2026Article
- The maternal PADI6-UHRF1-UBE2D complex regulates ubiquitination during oocyte maturation and embryogenesis.Nature structural & molecular biology · 2026Article
- Beckwith-Wiedemann spectrum (BWSp): an update on diagnosis, management, and follow-up from the scientific committee of the Italian BWSp association.Italian journal of pediatrics · 2025Review
- Highly variable genomic methylation in the Beckwith-Wiedemann syndrome associated with multi-locus imprinting disturbances.Clinical epigenetics · 2025Article
- Variants of NLRP genes encoding subcortical maternal complex components are linked to biparental placental mesenchymal dysplasia.Human genomics · 2025Article
- Subcortical Maternal Complex in Female Infertility: A Transition from Animal Models to Human Studies.Molecular biology reports · 2025Review
- A Maternal Loss-of-Function Variant in KHDC3L Gene Causes a Range of Adverse Pregnancy Outcomes: A Case Report.Molecular genetics & genomic medicine · 2025Article
- Novel variants in PADI6 genes cause female infertility due to early embryo arrest.Journal of assisted reproduction and genetics · 2024Article
- Structural insight into the function of human peptidyl arginine deiminase 6.Computational and structural biotechnology journal · 2024Article
- Methylation patterns at the adjacent CpG sites within enhancers are a part of cell identity.Epigenetics & chromatin · 2024Article
- Comprehensive molecular and clinical findings in 29 patients with multi-locus imprinting disturbance.Clinical epigenetics · 2024Article
- Multi-locus imprinting disturbance (MLID): interim joint statement for clinical and molecular diagnosis.Clinical epigenetics · 2024Review
- A maternal-effectGenes & development · 2024Article
- Review
- The Landscape of Point Mutations in Human Protein Coding Genes Leading to Pregnancy Loss.International journal of molecular sciences · 2023Review
- First-time application of droplet digital PCR for methylation testing of the 11p15.5 imprinting regions.Molecular genetics & genomic medicine · 2023Article
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Authors and funding
13 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPADI6 is a component of the subcortical maternal complex, a group of proteins that is abundantly expressed in the oocyte cytoplasm, but is required for the correct development of early embryo. Maternal-effect variants of the subcortical maternal complex proteins are associated with heterogeneous diseases, including female infertility, hydatidiform mole, and imprinting disorders with multi-locus imprinting disturbance. While the involvement of PADI6 in infertility is well demonstrated, its role in imprinting disorders is less well established.
resultsWe have identified by whole-exome sequencing analysis four cases of Beckwith-Wiedemann syndrome with multi-locus imprinting disturbance whose mothers are carriers of PADI6 variants. In silico analysis indicates that these variants result in loss of function, and segregation analysis suggests they act as either recessive or dominant-negative maternal-effect mutations. Genome-wide methylation analysis revealed heterogeneous and extensively altered methylation profiles of imprinted loci in the patients, including two affected sisters, but not in their healthy siblings.
conclusionOur results firmly establish the role of PADI6 in imprinting disorders. We report loss-of-function maternal-effect variants of PADI6 that are associated with heterogeneous multi-locus imprinting disturbances in the progeny. The rare finding of two siblings affected by Beckwith-Wiedemann syndrome suggests that in some cases, familial recurrence risk of these variants may be high. However, the heterogeneous phenotypes of the other pedigrees suggest that altered oocyte PADI6 function results in stochastic maintenance of methylation imprinting with unpredictable consequences on early embryo health.
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