TY - JOUR
T1 - De novo and inherited variants in ZNF292 underlie a neurodevelopmental disorder with features of autism spectrum disorder
AU - Undiagnosed Diseases Network,
AU - University of Washington Center for Mendelian Genomics (UW-CMG),
AU - Mirzaa, Ghayda M.
AU - Chong, Jessica X.
AU - Piton, Amélie
AU - Popp, Bernt
AU - Foss, Kimberly
AU - Guo, Hui
AU - Harripaul, Ricardo
AU - Xia, Kun
AU - Scheck, Joshua
AU - Aldinger, Kimberly A.
AU - Sajan, Samin A.
AU - Tang, Sha
AU - Bonneau, Dominique
AU - Beck, Anita
AU - White, Janson
AU - Mahida, Sonal
AU - Harris, Jacqueline
AU - Smith-Hicks, Constance
AU - Hoyer, Juliane
AU - Zweier, Christiane
AU - Reis, André
AU - Thiel, Christian T.
AU - Jamra, Rami Abou
AU - Zeid, Natasha
AU - Yang, Amy
AU - Farach, Laura S.
AU - Walsh, Laurence
AU - Payne, Katelyn
AU - Rohena, Luis
AU - Velinov, Milen
AU - Ziegler, Alban
AU - Schaefer, Elise
AU - Gatinois, Vincent
AU - Geneviève, David
AU - Simon, Marleen E.H.
AU - Kohler, Jennefer
AU - Rotenberg, Joshua
AU - Wheeler, Patricia
AU - Larson, Austin
AU - Ernst, Michelle E.
AU - Akman, Cigdem I.
AU - Westman, Rachel
AU - Blanchet, Patricia
AU - Schillaci, Lori Anne
AU - Vincent-Delorme, Catherine
AU - Gripp, Karen W.
AU - Mattioli, Francesca
AU - Guyader, Gwenaël Le
AU - Gerard, Bénédicte
AU - Mathieu-Dramard, Michèle
N1 - Publisher Copyright:
© 2019, American College of Medical Genetics and Genomics.
PY - 2020/3/1
Y1 - 2020/3/1
N2 - 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.
AB - 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.
KW - ZNF292
KW - autism spectrum disorders
KW - exome sequencing
KW - intellectual disability
KW - next-generation sequencing
UR - http://www.scopus.com/inward/record.url?scp=85075030020&partnerID=8YFLogxK
U2 - 10.1038/s41436-019-0693-9
DO - 10.1038/s41436-019-0693-9
M3 - Article
C2 - 31723249
AN - SCOPUS:85075030020
SN - 1098-3600
VL - 22
SP - 538
EP - 546
JO - Genetics in Medicine
JF - Genetics in Medicine
IS - 3
ER -