JARID2 haploinsufficiency is associated with a clinically distinct neurodevelopmental syndrome.

Autor: Verberne EA; Department of Clin Genet, Amsterdam UMC, Amsterdam Reproduction and Development Research Institute, University of Amsterdam, Amsterdam, The Netherlands., Goh S; Department of Clin Genet, Liverpool Hospital, Sydney, Australia., England J; Department of Pediatrics, University of Montreal, Montreal, QC, Canada., van Ginkel M; Department of Clin Genet, Amsterdam UMC, Amsterdam Reproduction and Development Research Institute, University of Amsterdam, Amsterdam, The Netherlands.; Department of Pediatrics, Dr. Horacio E. Oduber Hospital, Oranjestad, Aruba., Rafael-Croes L; Department of Pediatrics, Dr. Horacio E. Oduber Hospital, Oranjestad, Aruba., Maas S; Department of Clin Genet, Amsterdam UMC, Amsterdam Reproduction and Development Research Institute, University of Amsterdam, Amsterdam, The Netherlands., Polstra A; Department of Clin Genet, Amsterdam UMC, Amsterdam Reproduction and Development Research Institute, University of Amsterdam, Amsterdam, The Netherlands., Zarate YA; Section of Genetics and Metabolism, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA., Bosanko KA; Section of Genetics and Metabolism, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA., Pechter KB; Division of Genomic Diagnostics, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Bedoukian E; Roberts Individualized Medical Genetics Center and the Division of Hum Genet, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Izumi K; Roberts Individualized Medical Genetics Center and the Division of Hum Genet, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Chaudhry A; Department of Laboratory Medicine and Genetics, Trillium Health Partners, Mississauga, ON, Canada.; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada., Robin NH; Department of Genetics, University of Alabama at Birmingham (UAB), Birmingham, AL, USA., Boothe M; Department of Genetics, University of Alabama at Birmingham (UAB), Birmingham, AL, USA., Lippa NC; Institute for Genomic Medicine, Columbia University Irving Medical Center, New York, NY, USA., Aggarwal V; Institute for Genomic Medicine, Columbia University Irving Medical Center, New York, NY, USA., De Vivo DC; Departments of Neurology and Pediatrics, Columbia University Irving Medical Center, New York, NY, USA., Lehman A; Department of Medical Genetics, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada., Study C; Department of Medical Genetics, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada., Stockler S; Department of Pediatrics, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada., Bruel AL; Équipe Génétique des Anomalies du Développement (GAD), CHU Dijon-Bourgogne, Dijon, France., Isidor B; Service de génétique médicale, CHU de Nantes, Nantes, France., Lemons J; Department of Pediatrics, UTHealth McGovern Medical School, Houston, TX, USA., Rodriguez-Buritica DF; Department of Pediatrics, UTHealth McGovern Medical School, Houston, TX, USA., Richmond CM; Victorian Clin Genet Services, Murdoch Children's Research Institute, Melbourne, VIC, Australia.; School of Medicine, Griffith University, Gold Coast, QLD, Australia., Stark Z; Victorian Clin Genet Services, Murdoch Children's Research Institute, Melbourne, VIC, Australia.; Department of Paediatrics, University of Melbourne, Melbourne, VIC, Australia., Agrawal PB; Divisions of Newborn Medicine and Genetics & Genomics, Department of Pediatrics, Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA, USA., Kooy RF; Department of Medical Genetics, University of Antwerp, Antwerp, Belgium., Meuwissen MEC; Department of Medical Genetics, University of Antwerp, Antwerp, Belgium.; Department of Medical Genetics, University Hospital Antwerp, Antwerp, Belgium., Koolen DA; Department of Hum Genet, Radboud Institute for Molecular Life Sciences and Donders Institute for Brain, Cognition and Behaviour, Radboud university medical center, Nijmegen, The Netherlands., Pfundt R; Department of Hum Genet, Radboud Institute for Molecular Life Sciences and Donders Institute for Brain, Cognition and Behaviour, Radboud university medical center, Nijmegen, The Netherlands., Lieden A; Department of Clin Genet, Karolinska University Hospital, Stockholm, Sweden.; Department of molecular medicine and surgery, Karolinska Institutet, Stockholm, Sweden., Anderlid BM; Department of Clin Genet, Karolinska University Hospital, Stockholm, Sweden.; Department of molecular medicine and surgery, Karolinska Institutet, Stockholm, Sweden., Glatz D; Département de Médecine, Faculté de médecine, Université de Montréal, and Centre de Recherche de l'Hôpital Maisonneuve-Rosemont, Montreal, QC, Canada., Mannens MMAM; Department of Clin Genet, Amsterdam UMC, Amsterdam Reproduction and Development Research Institute, University of Amsterdam, Amsterdam, The Netherlands., Bakshi M; Department of Clin Genet, Liverpool Hospital, Sydney, Australia., Mallette FA; Département de Médecine, Faculté de médecine, Université de Montréal, and Centre de Recherche de l'Hôpital Maisonneuve-Rosemont, Montreal, QC, Canada., van Haelst MM; Department of Clin Genet, Amsterdam UMC, Amsterdam Reproduction and Development Research Institute, University of Amsterdam, Amsterdam, The Netherlands. m.vanhaelst@amsterdamumc.nl., Campeau PM; Department of Pediatrics, University of Montreal, Montreal, QC, Canada. p.campeau@umontreal.ca.
Jazyk: angličtina
Zdroj: Genetics in medicine : official journal of the American College of Medical Genetics [Genet Med] 2021 Feb; Vol. 23 (2), pp. 374-383. Date of Electronic Publication: 2020 Oct 20.
DOI: 10.1038/s41436-020-00992-z
Abstrakt: Purpose: JARID2, located on chromosome 6p22.3, is a regulator of histone methyltransferase complexes that is expressed in human neurons. So far, 13 individuals sharing clinical features including intellectual disability (ID) were reported with de novo heterozygous deletions in 6p22-p24 encompassing the full length JARID2 gene (OMIM 601594). However, all published individuals to date have a deletion of at least one other adjoining gene, making it difficult to determine if JARID2 is the critical gene responsible for the shared features. We aim to confirm JARID2 as a human disease gene and further elucidate the associated clinical phenotype.
Methods: Chromosome microarray analysis, exome sequencing, and an online matching platform (GeneMatcher) were used to identify individuals with single-nucleotide variants or deletions involving JARID2.
Results: We report 16 individuals in 15 families with a deletion or single-nucleotide variant in JARID2. Several of these variants are likely to result in haploinsufficiency due to nonsense-mediated messenger RNA (mRNA) decay. All individuals have developmental delay and/or ID and share some overlapping clinical characteristics such as facial features with those who have larger deletions involving JARID2.
Conclusion: We report that JARID2 haploinsufficiency leads to a clinically distinct neurodevelopmental syndrome, thus establishing gene-disease validity for the purpose of diagnostic reporting.
Databáze: MEDLINE
Externí odkaz: