Two de novo missense variants in the USH2A gene were identified in ASD probands from the Autism Sequencing Consortium (Neale et al., 2012) and the Simons Simplex Collection (Iossifov et al., 2014); one of these variants was later determined to be a postzygotic mosaic mutation (PZM) in Lim et al., 2017. A second non-synonymous PZM in this gene was identified in an ASD proband in Lim et al., 2017; comparison with a background set of 84,448 privately inherited variants demonstrated that this gene harbored more PZMs than expected based on background rates (/571 observed vs. /84,448 expected; hypergeometric P-value of 0.023). Biallelic variants in the USH2A gene have also been identified in individuals diagnosed with ASD (Xiong et al., 2019; Doan et al., 2019).
Molecular Function
This gene encodes a protein that contains laminin EGF motifs, a pentaxin domain, and many fibronectin type III motifs. The protein is found in the basement membrane, and may be important in development and homeostasis of the inner ear and retina. Mutations within this gene have been associated with Usher syndrome type IIa and retinitis pigmentosa.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Patterns and rates of exonic de novo mutations in autism spectrum disorders.
