Journal article
Maternal variants in NLRP and other maternal effect proteins are associated with multilocus imprinting disturbance in offspring
Journal of Medical Genetics, Vol.55(7), pp.497-504
2018
Abstract
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.
Details
- Title
- Maternal variants in NLRP and other maternal effect proteins are associated with multilocus imprinting disturbance in offspring
- Authors/Creators
- M. Begemann (Author/Creator) - RWTH Aachen UniversityF.I. Rezwan (Author/Creator) - University of SouthamptonJ. Beygo (Author/Creator) - University of Duisburg-EssenL.E. Docherty (Author/Creator) - University of EdinburghJ. Kolarova (Author/Creator) - Universität UlmC. Schroeder (Author/Creator) - University of Duisburg-EssenK. Buiting (Author/Creator) - University of Duisburg-EssenK. Chokkalingam (Author/Creator) - Nottingham University Hospitals NHS TrustF. Degenhardt (Author/Creator) - University of BonnE.L. Wakeling (Author/Creator) - Ealing Hospital NHS TrustS. Kleinle (Author/Creator) - Medical Genetics CenterD. González Fassrainer (Author/Creator)B. Oehl-Jaschkowitz (Author/Creator) - Praxis für HumangenetikC.L.S Turner (Author/Creator) - Phillips Exeter AcademyM. Patalan (Author/Creator) - Pomeranian Medical UniversityM. Gizewska (Author/Creator) - Pomeranian Medical UniversityG. Binder (Author/Creator) - University Children's Hospital TübingenC.T. Bich Ngoc (Author/Creator)V. Chi Dung (Author/Creator)S.G. Mehta (Author/Creator)G. Baynam (Author/Creator) - The University of Western AustraliaJ.P. Hamilton-Shield (Author/Creator) - Bristol Population Health Science InstituteS. Aljareh (Author/Creator) - University of SouthamptonO. Lokulo-Sodipe (Author/Creator) - University of SouthamptonR. Horton (Author/Creator) - University of SouthamptonR. Siebert (Author/Creator) - Universität UlmM. Elbracht (Author/Creator) - RWTH Aachen UniversityI.K. Temple (Author/Creator) - University of SouthamptonT. Eggermann (Author/Creator) - RWTH Aachen UniversityD.J.G. Mackay (Author/Creator) - University of Southampton
- Publication Details
- Journal of Medical Genetics, Vol.55(7), pp.497-504
- Publisher
- BMJ Group
- Identifiers
- 991005544005607891
- Murdoch Affiliation
- Murdoch University
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.186 Chromosome Disorders
- 1.186.1533 Genomic Imprinting
- Web Of Science research areas
- Genetics & Heredity
- ESI research areas
- Clinical Medicine