Germline variants in genes of the subcortical maternal complex and Multilocus Imprinting Disturbance are associated with miscarriage/infertility or Beckwith–Wiedemann progeny
Pierpaola Tannorella, Luciano Calzari, Cecilia Daolio, Ester Mainini, Alessandro Vimercati, Davide Gentilini, Fiorenza Soli, Annalisa Pedrolli, Maria Teresa Bonati, Lidia Larizza, Silvia Russo
Abstract
Beckwith-Wiedemann syndrome (BWS, OMIM # 130650) is an imprinting disorder, associated with overgrowth and increased risk of embryonal tumors. Patients carrying hypomethylation in the KCNQ1OT1:TSS DMR (11p15.5) show MLID (Multilocus Imprinting Disturbance) upon epimutations at other imprinted regions. Few cases of BWS MLID's mothers with biallelic pathogenetic variants in maternal effect genes, mainly components of the subcortical maternal complex, are reported. We describe two families, one with a history of conception difficulties with a novel homozygous nonsense NLRP2 variant and another experiencing 8 miscarriages with a compound heterozygous PADI6 variant.