RT Journal Article SR Electronic T1 Maternal variants in NLRP and other maternal effect proteins are associated with multilocus imprinting disturbance in offspring JF Journal of Medical Genetics JO J Med Genet FD BMJ Publishing Group Ltd SP 497 OP 504 DO 10.1136/jmedgenet-2017-105190 VO 55 IS 7 A1 Matthias Begemann A1 Faisal I Rezwan A1 Jasmin Beygo A1 Louise E Docherty A1 Julia Kolarova A1 Christopher Schroeder A1 Karin Buiting A1 Kamal Chokkalingam A1 Franziska Degenhardt A1 Emma L Wakeling A1 Stephanie Kleinle A1 Daniela González Fassrainer A1 Barbara Oehl-Jaschkowitz A1 Claire L S Turner A1 Michal Patalan A1 Maria Gizewska A1 Gerhard Binder A1 Can Thi Bich Ngoc A1 Vu Chi Dung A1 Sarju G Mehta A1 Gareth Baynam A1 Julian P Hamilton-Shield A1 Sara Aljareh A1 Oluwakemi Lokulo-Sodipe A1 Rachel Horton A1 Reiner Siebert A1 Miriam Elbracht A1 Isabel Karen Temple A1 Thomas Eggermann A1 Deborah J G Mackay YR 2018 UL http://jmg.bmj.com/content/55/7/497.abstract AB Background Genomic imprinting results from the resistance of germline epigenetic marks to reprogramming in the early embryo for a small number of mammalian genes. Genetic, epigenetic or environmental insults that prevent imprints from evading reprogramming may result in imprinting disorders, which impact growth, development, behaviour and metabolism. We aimed to identify genetic defects causing imprinting disorders by whole-exome sequencing in families with one or more members affected by multilocus imprinting disturbance.Methods Whole-exome sequencing was performed in 38 pedigrees where probands had multilocus imprinting disturbance, in five of whom maternal variants in NLRP5 have previously been found.Results We now report 15 further pedigrees in which offspring had disturbance of imprinting, while their mothers had rare, predicted-deleterious variants in maternal effect genes, including NLRP2, NLRP7 and PADI6. As well as clinical features of well-recognised imprinting disorders, some offspring had additional features including developmental delay, behavioural problems and discordant monozygotic twinning, while some mothers had reproductive problems including pregnancy loss.Conclusion The identification of 20 putative maternal effect variants in 38 families affected by multilocus imprinting disorders adds to the evidence that maternal genetic factors affect oocyte fitness and thus offspring development. Testing for maternal-effect genetic variants should be considered in families affected by atypical imprinting disorders.