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

Genet Med 2020 Mar 14;22(3):538-546. Epub 2019 Nov 14.

Division of Genetic Medicine, Department of Pediatrics, University of Washington School of Medicine, Seattle, WA, USA.

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.

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41436-019-0693-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7060121PMC
March 2020
5 Reads

Publication Analysis

Top Keywords

neurodevelopmental disorder
12
variants znf292
12
spectrum disorder
8
zinc finger
8
neurodevelopmental features
8
features including
8
including asd
8
inherited variants
8
finger protein
8
autism spectrum
8
znf292 variants
8
neurodevelopmental
6
variants
6
znf292
6
spectrum
5
disorder
5
sequencing data
4
data analyzed
4
characterize canonical
4
phenotype examine
4

References

(Supplied by CrossRef)

JX Chong et al.
Genet Med 2016

J Ligt de et al.
N Engl J Med 2012

K Kochinke et al.
Am J Hum Genet 2016

BJ O’Roak et al.
Nat Genet 2011

SM Lipkin et al.
Genes Dev 1993

H Takeda et al.
Nat Genet 2015

AA Philippakis et al.
Hum Mutat 2015

H Guo et al.
Mol Autism 2018

B Popp et al.
Eur J Hum Genet 2017

P Rentzsch et al.
Nucleic Acids Res 2019

S Richards et al.
Genet Med 2015

Similar Publications