1. Genomic duplication in the 19q13.42 imprinted region identified as a new genetic cause of intrauterine growth restriction
- Author
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Pierre-Simon Jouk, Patrick Lorès, Gaëlle Vieville, Véronique Satre, Radu Harbuz, Aurélie Truffot, Graciane Petre, Daniel Vaiman, Pierre F. Ray, Hervé Sartelet, Aminata Touré, François Berger, Brice Poreau, Sandrine Brandeis, Florence Amblard, Guillaume Martinez, Marie Bidart, Françoise Devillard, Charles Coutton, BrainTech Laboratory [CHU Grenoble Alpes - Inserm U1205], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA)-Centre Hospitalier Universitaire Grenoble Alpes (CHU Grenoble Alpes), Université Grenoble Alpes (UGA), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire [Grenoble] (CHU), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Service Génétique Médicale [CHU Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), BrainTech Laboratory [CHU Grenoble Alpes - Inserm U1205] (Brain Tech Lab ), CHU Grenoble-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), and Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])
- Subjects
Adult ,0301 basic medicine ,[SDV]Life Sciences [q-bio] ,Biopsy ,Intrauterine growth restriction ,Biology ,Ultrasonography, Prenatal ,Epigenesis, Genetic ,Genomic Imprinting ,03 medical and health sciences ,Pregnancy ,Gene Duplication ,Placenta ,Gene duplication ,Genetics ,medicine ,Humans ,Genetic Predisposition to Disease ,Genetic Testing ,Allele ,Gene ,ComputingMilieux_MISCELLANEOUS ,Genetic Association Studies ,reproductive and urinary physiology ,Genetics (clinical) ,Fetus ,Fetal Growth Retardation ,Microarray analysis techniques ,medicine.disease ,Immunohistochemistry ,Neoplasm Proteins ,DNA-Binding Proteins ,030104 developmental biology ,medicine.anatomical_structure ,embryonic structures ,Female ,Genomic imprinting ,Chromosomes, Human, Pair 19 - Abstract
We report findings from a male fetus of 26 weeks' gestational age with severe isolated intrauterine growth restriction (IUGR). Chromosomal microarray analysis (CMA) on amniotic fluid cells revealed a 1.06-Mb duplication in 19q13.42 inherited from the healthy father. This duplication contains 34 genes including ZNF331, a gene encoding a zinc-finger protein specifically imprinted (paternally expressed) in the placenta. Study of the ZNF331 promoter by methylation-specific-multiplex ligation-dependent probe amplification showed that the duplicated allele was not methylated in the fetus unlike in the father's genome, suggesting both copies of the ZNF331 gene are expressed in the fetus. The anti-ZNF331 immunohistochemical analysis confirmed that ZNF331 was expressed at higher levels in renal and placental tissues from this fetus compared to controls. Interestingly, ZNF331 expression levels in the placenta have previously been reported to inversely correlate with fetal growth parameters. The original observation presented in this report showed that duplication of ZNF331 could be a novel genetic cause of isolated IUGR and underlines the usefulness of CMA to investigate the genetic causes of isolated severe IUGR.
- Published
- 2018
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