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

TitleDe novo and inherited variants in ZNF292 underlie a neurodevelopmental disorder with features of autism spectrum disorder.
Publication TypeJournal Article
Year of Publication2019
AuthorsMirzaa, GM, Chong, JX, Piton, A, Popp, B, Foss, K, Guo, H, Harripaul, R, Xia, K, Scheck, J, Aldinger, KA, Sajan, SA, Tang, S, Bonneau, D, Beck, A, White, J, Mahida, S, Harris, J, Smith-Hicks, C, Hoyer, J, Zweier, C, Reis, A, Thiel, CT, Jamra, RAbou, Zeid, N, Yang, A, Farach, LS, Walsh, L, Payne, K, Rohena, L, Velinov, M, Ziegler, A, Schaefer, E, Gatinois, V, Geneviève, D, Simon, MEH, Kohler, J, Rotenberg, J, Wheeler, P, Larson, A, Ernst, ME, Akman, CI, Westman, R, Blanchet, P, Schillaci, L-A, Vincent-Delorme, C, Gripp, KW, Mattioli, F, Le Guyader, G, Gerard, B, Mathieu-Dramard, M, Morin, G, Sasanfar, R, Ayub, M, Vasli, N, Yang, S, Person, R, Monaghan, KG, Nickerson, DA, van Binsbergen, E, Enns, GM, Dries, AM, Rowe, LJ, Tsai, ACH, Svihovec, S, Friedman, J, Agha, Z, Qamar, R, Rodan, LH, Martinez-Agosto, J, Ockeloen, CW, Vincent, M, Sunderland, WJames, Bernstein, JA, Eichler, EE, Vincent, JB, Bamshad, MJ
Corporate AuthorsUndiagnosed Diseases Network,, University of Washington Center for Mendelian Genomics (UW-CMG),
JournalGenet Med
Date Published2019 Nov 14

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.

Alternate JournalGenet. Med.
PubMed ID31723249
Grant ListR01 MH101221 / MH / NIMH NIH HHS / United States
K08NS092898 / NS / NINDS NIH HHS / United States
31671114 / / the Agence de la Biomédecine and the CREGEMES, the Canadian Institutes of Health Research /
UM1 HG006493 / HG / NHGRI NIH HHS / United States