Maternal Genes and Epimutations: Beckwith-Wiedemann Syndrome & Reproductive Risks

Pathogenic variants in subcortical maternal complex (SCMC) have been identified not only in mothers of Beckwith-Wiedemann syndrome (BWS) babies but also in women with reproductive disturbances such as failed pregnancy attempts and recurrent pregnancy loss. Based on the higher incidence of BWS in children born from Assisted Reproductive Technology (ART), this project aims to investigate incidence and molecular mechanism of pathogenic variants of SCMC in women with reproductive disorders. Study objectives will be (i) assess the incidence of these variants as a cause of differences in reproductive outcomes in the infertile female population and mothers of children with BWS; (ii) identify methylation changes in women with reproductive problems including those with offspring affected by BWS; (iii) determine the molecular causes underlying female infertility and imprinting disorder associated with damaging SCMC gene variants by employing a mouse model.

NCT Number	NCT06346418
Lead Sponsor	Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico Collaborators: Istituto Auxologico Italiano, University of Campania Luigi Vanvitelli, Federico II University
Conditions	Beckwith-Wiedemann Syndrome
Enrollment	208 participants
Start Date	2023-05-19
Primary Completion	2025-12 (estimated)
Study Completion	2026-01 (estimated)
Updated on ClinicalTrials.gov	2025-05-02