 |
| MRI findings |
 |
| Features of ZNF292 neurodevelopmental disorder |
P.s. Thankful that I could contribute
De Novo and Inherited Variants in ZNF292 Underlie a Neurodevelopmental Disorder With Features of Autism Spectrum Disorder
Article here
Abstract
Purpose: Intellectual disability (ID) and autism spectrum disorder (ASD) are genetically heterogeneous neurodevelopmental disorders. We sought to delineate the clinical, molecular, and neuroimaging spectrum of a novel neurodevelopmental disorder caused by variants in the zinc finger protein 292 gene (ZNF292).
Methods: We ascertained a cohort of 28 families with ID due to putatively pathogenic ZNF292 variants that were identified via targeted and exome sequencing. Available data were analyzed to characterize the canonical phenotype and examine genotype-phenotype relationships.
Results: Probands presented with ID as well as a spectrum of neurodevelopmental features including ASD, among others. All ZNF292 variants were de novo, except in one family with dominant inheritance. ZNF292 encodes a highly conserved zinc finger protein that acts as a transcription factor and is highly expressed in the developing human brain supporting its critical role in neurodevelopment.
Conclusion: De novo and dominantly inherited variants in ZNF292 are associated with a range of neurodevelopmental features including ID and ASD. The clinical spectrum is broad, and most individuals present with mild to moderate ID with or without other syndromic features. Our results suggest that variants in ZNF292 are likely a recurrent cause of a neurodevelopmental disorder manifesting as ID with or without ASD.
Keywords: ZNF292; autism spectrum disorders; exome sequencing; intellectual disability; next-generation sequencing.
“ZNF292 encodes a highly conserved zinc finger protein that acts as a transcription factor. ZNF292 is composed of eight exons, the last of which is the largest and encodes all 16 highly conserved zinc fingers of the predicted 2723-residue protein (canonical transcript in GenBank: NM_015021.2). Three of these zinc fingers (10–12) bind DNA at the promoter of growth hormone where it cooperates with POU1F1, a member of the POU family of transcription factors known to activate transcription in somatotrophs.5 Accordingly, the ZNF292 protein was originally described as an enhancer of growth hormone (GH) expression in the pituitary gland of a rat animal model.5 Its role was further delineated as a tumor suppressor with critical roles in tumor development and progression.6 However, the role of ZNF292 in neurodevelopment is virtually unknown.”
Ghayda M. Mirzaa, MD 1,2,3, Jessica X. Chong, PhD2,3, Amélie Piton, MD4,5, Bernt Popp, MD6, Kimberly Foss, MS1, Hui Guo, PhD7, Ricardo Harripaul, MSc8,9, Kun Xia, PhD7, Joshua Scheck, BS1, Kimberly A. Aldinger, PhD1, Samin A. Sajan, PhD10, Sha Tang, PhD11, Dominique Bonneau, MD, PhD12,13, Anita Beck, MD, PhD2, Janson White, PhD14, Sonal Mahida, MGC, CGC15, Jacqueline Harris, MD15, Constance Smith-Hicks, MD, PhD15, Juliane Hoyer, MD6, Christiane Zweier, MD, PhD6, André Reis, MD6, Christian T. Thiel, MD6, Rami Abou Jamra, MD16, Natasha Zeid, MS, CGC17, Amy Yang, MD18,
Laura S. Farach, MD19, Laurence Walsh, MD20, Katelyn Payne, MS, CGC20, Luis Rohena, MD21,22,
Milen Velinov, MD, PhD23, Alban Ziegler, MD12,24, Elise Schaefer, MD, PhD25,
Vincent Gatinois, MD, PhD26,27,28, David Geneviève, MD, PhD26,27,28, Marleen E. H. Simon, MD29, Jennefer Kohler, MS30, Joshua Rotenberg, MD31, Patricia Wheeler, MD32, Austin Larson, MD33, Michelle E. Ernst, MS, CGC34, Cigdem I. Akman, MD34,35, Rachel Westman, MS, CGC36,
Patricia Blanchet, MD27, Lori-Anne Schillaci, MD37, Catherine Vincent-Delorme, MD38,
Karen W. Gripp, MD39, Francesca Mattioli, PhD40, Gwenaël Le Guyader, MD, PhD41,
Bénédicte Gerard, MD4, Michèle Mathieu-Dramard, MD42, Gilles Morin, MD43, Roksana Sasanfar, MD43, Muhammad Ayub, MD44, Nasim Vasli, PhD45, Sandra Yang, MS, CGC46, Rick Person, PhD46,
Kristin G. Monaghan, PhD46, Deborah A. Nickerson, PhD14, Ellen van Binsbergen, M Gregory M. Enns, MBChB30,47, Annika M. Dries, BS30, Leah J. Rowe, MS, CGC33, Anne C. H. Tsai, MD33, Shayna Svihovec, MS, CGC33, Jennifer Friedman, MD48,49, Zehra Agha, MD50, Raheel Qamar, MD50, Lance H. Rodan, MD51,52, Julian Martinez-Agosto, MD, PhD53, Charlotte W. Ockeloen, MD54,
Marie Vincent, MD55, William James Sunderland, PhD56, Jonathan A. Bernstein, MD, PhD30,47, Undiagnosed Diseases Network, Evan E. Eichler, PhD14,58, John B. Vincent, PhD8,9,
University of Washington Center for Mendelian Genomics (UW-CMG), Michael J. Bamshad, MD2,3
1Center for Integrative Brain Research, Seattle Children’s Research Institute, Seattle, WA, USA; 2Division of Genetic Medicine, Department of Pediatrics, University of Washington School of Medicine, Seattle, WA, USA; 3Brotman Baty Institute for Precision Medicine, Seattle, Washington, USA; 4Molecular Genetic Unit, Strasbourg University Hospital, Strasbourg, France; 5Institute of Genetics and Molecular and Cellular Biology, Université de Strasbourg, Illkirch, France; 6Institute of Human Genetics, University Hospital Elrangen, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Erlangen, Germany; 7Center for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China; 8The Campbell Family Mental Health Research Institute, Centre for Addiction & Mental Health (CAMH), Toronto, ON, Canada; 9Institute of Medical Science, University of Toronto, Toronto, ON, Canada; 10Department of Clinical Genomics, Ambry Genetics, Aliso Viejo, CA, USA; 11WuXi NextCODE, Cambridge, MA, USA; 12Département de Biochimie et de Génétique, CHU d’Angers, Angers, France; 13UMR INSERM 1083 CNRS 6015, Angers, France; 14Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA; 15Department of Neurogenetics, Kennedy Krieger Institute, Baltimore, MD, USA; 16Institute of Human Genetics, University Medical Center Leipzig, Leipzig, Germany; 17Yale New Haven Health, New Haven, CT, USA; 18Department of Molecular and Medical Genetics, Oregon Health and Science University, Portland, OR, USA; 19Department of Pediatrics, McGovern Medical School at the University of Texas Health Sciences Center, Houston, TX, USA; 20Indiana University Health at Riley Hospital for Children, Indianapolis, IN, USA; 21Division of Genetics, Department of Pediatrics, San Antonio Military Medical Center, San Antonio, TX, USA; 22Department of Pediatrics, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA; 23New York State Institute for Basic Research in Developmental Disability, NY, Staten Island, USA; 24Service de Génétique Médicale, Centre hospitalier, Le Mans, France; 25Service de Génétique Médicale, Hôpitaux Universitaires de Strasbourg, Institut de Génétique Médicale d’Alsace, Strasbourg, France; 26Service de génétique clinique, Département de Génétique Médicale, Maladies Rares et Médecine Personnalisée, Strasbourg, France; 27Centre de Référence Maladies Rares Anomalies du Développement et Syndromes Malformatifs Sud-Ouest Occitanie Réunion, Hôpital Arnaud de Villeneuve, Montpellier, France; 28Université Montpellier, Unité Inserm U1183, Montpellier, France; 29Department of Genetics, University Medical Center Utrecht, Utrecht, The Netherlands; 30Stanford Center for Undiagnosed Diseases, Stanford University, Stanford, CA, USA; 31Memorial Hermann Memorial City Medical Center, Houston, TX, USA; Arnold Palmer Hospital for Children, Orlando, FL, USA; 33Section of Genetics, Department of Pediatrics, University of Colorado School of Medicine and Children’s Hospital Colorado, Aurora, CO, USA; 34Institute for Genomic Medicine, Columbia University Irving Medical Center, New York, NY, USA; 35Division of Pediatric Neurology, Columbia University Irving Medical Center, New York, NY, USA; 36Division of Genetics, St. Luke’s Clinic, Boise, ID, USA; 37Department of Genetics and Genome Sciences, Case Western Reserve University, University Hospitals Cleveland Medical Center, Cleveland, OH, USA; 38Service de Génétique Clinique Guy Fontaine Centre de référence maladies rares Anomalies du dévelopement, Hôpital Jeanne de Flandre Lille, Lille, France; 39Department of Pediatrics, AI duPont Hospital, DE, Wilmington, USA; 40Institut de Genetique et de Biologie Moleculaire et Cellulaire, Illkirch-Graffenstaden, Lille, France; 41Service de Génétique Clinique, Centre de compétence Maladies rares Anomalies du dévelopement, CHU de Poitiers, Poitiers, France; 42Service de Génétique Clinique Centre de référence maladies rares Anomalies du dévelopement, CHU Amiens-Picardie, Amiens, France; 43Children’s Medical Center, UMass Memorial Medical Center, Worcester, MA, USA; 44Department of Psychiatry, Queen’s University, Kingston, ON, Canada; 45Division of Clinical & Metabolic Genetics, Hospital for Sick Children, Toronto, ON, Canada; 46GeneDx, Gaithersburg, MD, USA; Division of Medical Genetics, Department of Pediatrics, Lucile Packard Children’s Hospital, Stanford University, Stanford, CA, USA; 48Departments of Neurosciences and Pediatrics, University of California San Diego and Division of Neurology, Rady Children’s Hospital, San Diego, CA, USA; Rady Children’s Institute for Genomic Medicine, San Diego, CA, USA; 50Department of Biosciences, COMSATS University, Islamabad, Pakistan; 51Division of Genetics and Genomics, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA; 52Department of Neurology, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA; 53David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; 54Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands; 55CHU de Nantes, Service de génétique médicale, Nantes, France; 56University of Washington Foundation Board, University of Washington, Seattle, WA, USA; 57NIH Undiagnosed Diseases Network, Office of the Director and the National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA; 58Howard Hughes Medical Institute, University of Washington, Seattle, WA, USA.
No comments:
Post a Comment