Trans-acting genetic variants causing multilocus imprinting disturbance (MLID): common mechanisms and consequences

• DOI: 10.1186/s13148-022-01259-x
• Publication Date: 2022-03-16T13:02:45Z
• Authors: Thomas Eggermann; Elzem Yapici; Jet Bliek; Arrate Pereda; Matthias Begemann; Silvia Russo; Pierpaola Tannorella; Luciano Calzari; Guiomar Perez de ...; Paola Lombardi; I. Karen Temple; Deborah Mackay; Andrea Riccio; Masayo Kagami; Tsutomu Ogata; Pablo Lapunzina; David Monk; Eamonn R. Maher; Zeynep Tümer
• Keywords: Genomic Imprinting; Imprinting (psychology); Candidate gene; Differentially methylated regions

Imprinting disorders are a group of congenital diseases which characterized by molecular alterations affecting differentially methylated regions (DMRs). To date, at least twelve imprinting have been defined with overlapping but variable clinical features including growth and metabolic disturbances, cognitive dysfunction, abdominal wall defects asymmetry. In general, single specific DMR is affected in an individual given disorder, there growing number reports on individuals so-called multilocus disturbances (MLID), where aberrant marks (most commonly loss methylation) occur multiple DMRs. However, as the literature fragmented, we reviewed data 55 previously reported or newly identified MLID families putative pathogenic variants maternal effect genes (NLRP2, NLRP5, NLRP7, KHDC3L, OOEP, PADI6) other candidate (ZFP57, ARID4A, ZAR1, UHRF1, ZNF445).In families, total 68 different were (7 NLRP2, 16 7 17 PADI6, 15 ZFP57, variant each KHDC3L ZNF445). Clinical diagnoses offspring included Beckwith-Wiedemann syndrome spectrum, Silver-Russell transient neonatal diabetes mellitus, they suspected for disorder (undiagnosed). Some had recurrent pregnancy loss.Genomic foetal causing allow insights into mechanisms behind cycle life, spatial temporal function factors involved oocyte maturation early development. Further basic research together identification new will enable better understanding link between reproductive issues such miscarriages preeclampsia carriers/families aneuploidy observed offsprings. The current knowledge can already be employed genetic counselling situations.