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 Begemann, Matthias A1 Rezwan, Faisal I A1 Beygo, Jasmin A1 Docherty, Louise E A1 Kolarova, Julia A1 Schroeder, Christopher A1 Buiting, Karin A1 Chokkalingam, Kamal A1 Degenhardt, Franziska A1 Wakeling, Emma L A1 Kleinle, Stephanie A1 González Fassrainer, Daniela A1 Oehl-Jaschkowitz, Barbara A1 Turner, Claire L S A1 Patalan, Michal A1 Gizewska, Maria A1 Binder, Gerhard A1 Bich Ngoc, Can Thi A1 Chi Dung, Vu A1 Mehta, Sarju G A1 Baynam, Gareth A1 Hamilton-Shield, Julian P A1 Aljareh, Sara A1 Lokulo-Sodipe, Oluwakemi A1 Horton, Rachel A1 Siebert, Reiner A1 Elbracht, Miriam A1 Temple, Isabel Karen A1 Eggermann, Thomas A1 Mackay, Deborah J G 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.