De novo and inherited variants in ZNF292 underlie a neurodevelopmental disorder with features of autism spectrum disorder

Ghayda M. Mirzaa; Jessica Chong; Amélie Piton; Bernt Popp; Kimberly Foss; Hui Guo; Ricardo Harripaul; Kun Xia; Joshua Scheck; Kimberly Aldinger; Samin Sajan; Sha Tang; Dominique Bonneau; Anita Beck; Janson J. White; Sonal Mahida; Jacqueline Harris; Constance Smith-Hicks; Juliane Hoyer; Christiane Zweier; Andre Reis; Christian Thiel; Rami Abou Jamra; Natasha Zeid; Amy Yang; Laura Farach; Laurence Walsh; Katelyn Payne; Luis Rohena; Milen Velinov; Alban Ziegler; Elise Schaefer; Vincent Gatinois; David Geneviève; Marleen Simon; Jennefer Kohler; Joshua Rotenberg; Patricia Wheeler; Austin Larson; Michelle Ernst; Cigdem Akman; Rachel Westman; Patricia Blanchet; Lori-Anne Schillaci; Catherine Vincent-Delorme; Karen Gripp; Francesca Mattioli; Gwenaël Le Guyader; Bénédicte Gérard; Michele Mathieu-Dramard; Gilles Morin; Roksana Sasanfar; Muhammad Ayub; Nasim Vasli; Sandra Yang; Rick Person; Kristin Monaghan; Deborah A Nickerson; Ellen van Binsbergen; Gregory M. Enns; Annika Dries; Leah Rowe; Anne Tsai; Shayna Svihovec; Jennifer Friedman; Zehra Agha; Raheel Qamar; Lance H Rodan; Julian Martinez-Agosto; Charlotte Ockeloen; Marie Vincent; William James Sunderland; Jonathan Bernstein; Evan Eichler; John B. Vincent; Michael Bamshad

doi:10.1038/s41436-019-0693-9

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De novo and inherited variants in ZNF292 underlie a neurodevelopmental disorder with features of autism spectrum disorder

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De novo and inherited variants in ZNF292 underlie a neurodevelopmental disorder with features of autism spectrum disorder

Ghayda M. Mirzaa, Jessica Chong, Amélie Piton, Bernt Popp, Kimberly Foss, Hui Guo, Ricardo Harripaul, Kun Xia, Joshua Scheck, Kimberly Aldinger, …

Genetics in Medicine, Vol.22(3), pp.538-546

03/2020

DOI: https://doi.org/10.1038/s41436-019-0693-9

PMCID: PMC7060121

Abstract

ZNF292

autism spectrum disorders

exome sequencing

intellectual disability

next-generation sequencing

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.

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Title: De novo and inherited variants in ZNF292 underlie a neurodevelopmental disorder with features of autism spectrum disorder
Creators - without role: Ghayda M. Mirzaa - University of Washington
Jessica Chong - Brotman Baty Institute
Amélie Piton - Institut de génétique et de biologie moléculaire et cellulaire
Bernt Popp - Friedrich-Alexander-Universität Erlangen-Nürnberg
Kimberly Foss - University of Washington
Hui Guo - Central South University
Ricardo Harripaul - University of Toronto
Kun Xia - Central South University
Joshua Scheck - University of Washington
Kimberly Aldinger
Samin Sajan - Ambry Genetics
Sha Tang - WuXi AppTec
Dominique Bonneau - Centre Hospitalier Universitaire d'Angers
Anita Beck - University of Washington
Janson J. White - University of Washington
Sonal Mahida - Kennedy Krieger Institute
Jacqueline Harris - Kennedy Krieger Institute
Constance Smith-Hicks - Kennedy Krieger Institute
Juliane Hoyer - Friedrich-Alexander-Universität Erlangen-Nürnberg
Christiane Zweier - Friedrich-Alexander-Universität Erlangen-Nürnberg
Andre Reis - Friedrich-Alexander-Universität Erlangen-Nürnberg
Christian Thiel - Friedrich-Alexander-Universität Erlangen-Nürnberg
Rami Abou Jamra - Leipzig University
Natasha Zeid - Yale New Haven Health System
Amy Yang - Oregon Health & Science University
Laura Farach - The University of Texas Health Science Center at Houston
Laurence Walsh - Riley Hospital for Children
Katelyn Payne - Riley Hospital for Children
Luis Rohena - The University of Texas Health Science Center at San Antonio
Milen Velinov - New York State Office for People With Developmental Disabilities
Alban Ziegler - Centre Hospitalier Universitaire d'Angers
Elise Schaefer - Hôpitaux Universitaires de Strasbourg
Vincent Gatinois - Université de Montpellier, Cell souches plasticité cellul régénérat tissulaire immuno des maladies inflamm - IRMB
David Geneviève - Université de Montpellier, Cell souches plasticité cellul régénérat tissulaire immuno des maladies inflamm - IRMB
Marleen Simon - University Medical Center Utrecht
Jennefer Kohler - Stanford University
Joshua Rotenberg - Memorial Hermann Memorial City Medical Center
Patricia Wheeler - Arnold Palmer Hospital for Children
Austin Larson - Children's Hospital Colorado
Michelle Ernst - Columbia University
Cigdem Akman - Columbia University
Rachel Westman - St. Luke's Clinic
Patricia Blanchet - Hôpital Arnaud de Villeneuve
Lori-Anne Schillaci - University Hospitals of Cleveland
Catherine Vincent-Delorme - Hôpital Jeanne de Flandre
Karen Gripp - Dupont Hospital
Francesca Mattioli - Institut de génétique et de biologie moléculaire et cellulaire
Gwenaël Le Guyader - Centre hospitalier universitaire de Poitiers = Poitiers University Hospital
Bénédicte Gérard - Université de Strasbourg
Michele Mathieu-Dramard - Centre Hospitalier Universitaire Amiens-Picardie
Gilles Morin - Children's Medical Center
Roksana Sasanfar - UMass Memorial Medical Center
Muhammad Ayub - Queen's University
Nasim Vasli - Hospital for Sick Children
Sandra Yang - GeneDx [Gaithersburg, MD, USA]
Rick Person - GeneDx [Gaithersburg, MD, USA]
Kristin Monaghan - GeneDx [Gaithersburg, MD, USA]
Deborah A Nickerson - University of Washington
Ellen van Binsbergen - University Medical Center Utrecht
Gregory M. Enns - Stanford University
Annika Dries - Stanford University
Leah Rowe - Children's Hospital Colorado
Anne Tsai - Children's Hospital Colorado
Shayna Svihovec - University of Colorado Denver
Jennifer Friedman - Rady Children's Hospital-San Diego
Zehra Agha - COMSATS University Islamabad
Raheel Qamar - COMSATS University Islamabad
Lance H Rodan - Boston Children's Hospital
Julian Martinez-Agosto - University of California, Los Angeles
Charlotte Ockeloen - Radboud University Nijmegen
Marie Vincent - Génétique Médicale & Génomique Fonctionelle
William James Sunderland - University of Washington
Jonathan Bernstein - Lucile Packard Children's Hospital
Evan Eichler - Howard Hughes Medical Institute
John B. Vincent - Centre for Addiction and Mental Health
Michael Bamshad - University of Washington
Publication Details: Genetics in Medicine, Vol.22(3), pp.538-546
Identifiers: 9933755009311
Academic Unit: Cell souches plasticité cellul régénérat tissulaire immuno des maladies inflamm - IRMB
Language: English
Resource Type: Journal article
Local Fields: hal-02543379