Role of Maternal Effect Genes and Epimutations in Beckwith-Wiedemann Syndrome and Adverse Reproductive Outcomes
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.
• Cohort 1: healthy women with offspring affected by BWS and peculiar reproductive history from our population of clinically and molecularly diagnosed BWS families;
• Cohort 2: women under 35 undergoing ART for infertility (defined as failure to achieve a pregnancy after 12 months or more of regular unprotected sexual intercourses) and unable to obtain a live birth after three completed cycles or after the transfer of at least 6 blastocysts;
• Cohort 3: women under 35, with RPL (defined as the loss of two or more pregnancies before 24 weeks of gestation).