TY - JOUR T1 - Maternal variants in <em>NLRP</em> and other maternal effect proteins are associated with multilocus imprinting disturbance in offspring JF - Journal of Medical Genetics JO - J Med Genet SP - 497 LP - 504 DO - 10.1136/jmedgenet-2017-105190 VL - 55 IS - 7 AU - Matthias Begemann AU - Faisal I Rezwan AU - Jasmin Beygo AU - Louise E Docherty AU - Julia Kolarova AU - Christopher Schroeder AU - Karin Buiting AU - Kamal Chokkalingam AU - Franziska Degenhardt AU - Emma L Wakeling AU - Stephanie Kleinle AU - Daniela González Fassrainer AU - Barbara Oehl-Jaschkowitz AU - Claire L S Turner AU - Michal Patalan AU - Maria Gizewska AU - Gerhard Binder AU - Can Thi Bich Ngoc AU - Vu Chi Dung AU - Sarju G Mehta AU - Gareth Baynam AU - Julian P Hamilton-Shield AU - Sara Aljareh AU - Oluwakemi Lokulo-Sodipe AU - Rachel Horton AU - Reiner Siebert AU - Miriam Elbracht AU - Isabel Karen Temple AU - Thomas Eggermann AU - Deborah J G Mackay Y1 - 2018/07/01 UR - http://jmg.bmj.com/content/55/7/497.abstract N2 - 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. ER -