例如："lncRNA", "apoptosis", "WRKY"

Maternal variants in NLRP and other maternal effect proteins are associated with multilocus imprinting disturbance in offspring.

J. Med. Genet.2018 Jul;55(7):497-504. Epub 2018 Mar 24
Matthias Begemann 1 , Faisal I Rezwan 2 , Jasmin Beygo 3 , Louise E Docherty 4 , Julia Kolarova 5 , Christopher Schroeder 3 , Karin Buiting 3 , Kamal Chokkalingam 6 , Franziska Degenhardt 7 , Emma L Wakeling 8 , Stephanie Kleinle 9 , Daniela González Fassrainer 9 , Barbara Oehl-Jaschkowitz 10 , Claire L S Turner 11 , Michal Patalan 12 , Maria Gizewska 12 , Gerhard Binder 13 , Can Thi Bich Ngoc 14 , Vu Chi Dung 14 , Sarju G Mehta 15 , Gareth Baynam 16 , Julian P Hamilton-Shield 17 , Sara Aljareh 2 , Oluwakemi Lokulo-Sodipe 18 , Rachel Horton 18 , Reiner Siebert 5 , Miriam Elbracht 1 , Isabel Karen Temple 18 , Thomas Eggermann 1 , Deborah J G Mackay 2
Matthias Begemann 1 , Faisal I Rezwan 2 , Jasmin Beygo 3 , Louise E Docherty 4 , Julia Kolarova 5 , Christopher Schroeder 3 , Karin Buiting 3 , Kamal Chokkalingam 6 , Franziska Degenhardt 7 , Emma L Wakeling 8 , Stephanie Kleinle 9 , Daniela González Fassrainer 9 , Barbara Oehl-Jaschkowitz 10 , Claire L S Turner 11 , Michal Patalan 12 , Maria Gizewska 12 , Gerhard Binder 13 , Can Thi Bich Ngoc 14 , Vu Chi Dung 14 , Sarju G Mehta 15 , Gareth Baynam 16 , Julian P Hamilton-Shield 17 , Sara Aljareh 2 , Oluwakemi Lokulo-Sodipe 18 , Rachel Horton 18 , Reiner Siebert 5 , Miriam Elbracht 1 , Isabel Karen Temple 18 , Thomas Eggermann 1 , Deborah J G Mackay 2
+ et al

[No authors listed]

Author information
  • 1 Institute of Human Genetics, RWTH Aachen University, Aachen, Germany.
  • 2 Faculty of Medicine, University of Southampton, Southampton, UK.
  • 3 Institute of Human Genetics, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
  • 4 MRC Human Genetics Unit, The Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
  • 5 Institute of Human Genetics, University of Ulm, Ulm, Germany.
  • 6 Department of Diabetic Medicine, Nottingham University Hospital NHS Trust, Nottingham, UK.
  • 7 Institute of Human Genetics, Bonn, Germany.
  • 8 North West Thames Regional Genetics Service, London North West Healthcare NHS Trust, London, UK.
  • 9 Medical Genetics Center München, München, Germany.
  • 10 Praxis für Humangenetik Homburg, Homburg, Germany.
  • 11 Peninsula Genetics Service, Royal Devon and Exeter Hospital, Exeter, UK.
  • 12 Department of Pediatrics, Endocrinology, Diabetology, Metabolic Diseases and Cardiology, Pomeranian Medical University, Szczecin, Poland.
  • 13 Pediatric Endocrinology, University Children's Hospital, Tübingen, Germany.
  • 14 Department of Medical Genetics, Metabolism and Endocrinology, The National Children's Hospital, Hanoi, Vietnam.
  • 15 Department of Clinical Genetics, Cambridge University Hospitals Trust, Cambridge, UK.
  • 16 Genetic Services of Western Australian and Western Australian Register of Developmental Anomalies, Perth, Western Australia, Australia.
  • 17 School of Clinical Sciences, University of Bristol, Bristol, UK.
  • 18 Wessex Clinical Genetics Service, University Hospital, Southampton, UK.

摘要

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 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.

KEYWORDS: Beckwith-Wiedemann syndrome, NLRP2, NLRP5, NLRP7, PADI6, Silver-Russell syndrome, genomic imprinting, multi-locus imprinting disorder

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