Phenotypic Profile of Children with ASD with Gene Disruptions in the Beta-Catenin Pathway

Friday, May 16, 2014: 4:54 PM
Marquis A (Marriott Marquis Atlanta)
R. K. Earl1, J. E. Elgin2, T. Ward2, A. Stevens1, J. Gerdts1 and R. Bernier1, (1)University of Washington, Seattle, WA, (2)University of Washington Autism Center, Seattle, WA
Background:   Autism spectrum disorder (ASD) is a genotypically and phenotypically complex disorder. Gene disruptions within the beta-catenin pathway have been associated with ASD (O’Roak et al, 2012). Beta-catenin plays a critical biological role in cell growth and differentiation, and is believed to be involved in synaptic formation as well as memory and learning processes (Maguschak & Ressler, 2012). Understanding the phenotypic profile that accompanies genetic mutations in this specific pathway can help to tease apart potential ASD subtypes that arise from different genetic disruptions. 

Objectives:  To explore the cognitive and behavioral phenotype as well as gender distribution of individuals with ASD who have a gene disruption in the beta-catenin pathway compared to affected individuals without this pathway mutation.

Methods:  Participants were 2557 children meeting strict criteria for ASD. 94 children (29 female) with disruptive mutations falling in a protein network within the beta-catenin pathway were compared to 2151 children (312 female) without gene disrupting mutations in this network. Groups were compared on nonverbal (NVIQ) and verbal IQ (VIQ), as well as parent-reported and clinician-observed measures of social impairment and repetitive behaviors as a function of gender.

Results:   Groups differed in gender rate, with a higher rate of females in the beta-catenin pathway group than the non-pathway group (c2(1, N=2557) = 25.9, p<.001). Children in the pathway group had lower nonverbal and verbal IQ scores relative to the non-pathway group (NVIQ: F(1,2552) = 21.7, p<.001, η2=.008; VIQ: F(1,2552) = 6.56, p=.010, η2=.003). There was an interaction between pathway status and gender, indicating a trend toward increased social impairment in males in the pathway group and no differences in females across groups (F(1,2421)=4.19, p=.041, η2=.002).

Conclusions:  Higher rates of females in the beta-catenin pathway group replicate previous findings of higher incidence of genetic mutations and copy number variations in females with ASD (Marshall et al, 2008). The phenotype of children with beta-catenin pathway disruption is characterized by significantly greater cognitive impairment and increased social impairment in males, echoing beta-catenin’s role in memory, learning, and socioaffective processes. Phenotypic subtyping such as this is a promising way to illuminate genotypic variations amongst individuals with ASD.

See more of: Genetics
See more of: Genetics