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Open Access 01-12-2014 | Research

A CTNNA3 compound heterozygous deletion implicates a role for αT-catenin in susceptibility to autism spectrum disorder

Authors: Elena Bacchelli, Fabiola Ceroni, Dalila Pinto, Silvia Lomartire, Maila Giannandrea, Patrizia D'Adamo, Elena Bonora, Piero Parchi, Raffaella Tancredi, Agatino Battaglia, Elena Maestrini

Published in: Journal of Neurodevelopmental Disorders | Issue 1/2014

Abstract

Background

Autism spectrum disorder (ASD) is a highly heritable, neurodevelopmental condition showing extreme genetic heterogeneity. While it is well established that rare genetic variation, both de novo and inherited, plays an important role in ASD risk, recent studies also support a rare recessive contribution.

Methods

We identified a compound heterozygous deletion intersecting the CTNNA3 gene, encoding αT-catenin, in a proband with ASD and moderate intellectual disability. The deletion breakpoints were mapped at base-pair resolution, and segregation analysis was performed. We compared the frequency of CTNNA3 exonic deletions in 2,147 ASD cases from the Autism Genome Project (AGP) study versus the frequency in 6,639 controls. Western blot analysis was performed to get a quantitative characterisation of Ctnna3 expression during early brain development in mouse.

Results

The CTNNA3 compound heterozygous deletion includes a coding exon, leading to a putative frameshift and premature stop codon. Segregation analysis in the family showed that the unaffected sister is heterozygote for the deletion, having only inherited the paternal deletion. While the frequency of CTNNA3 exonic deletions is not significantly different between ASD cases and controls, no homozygous or compound heterozygous exonic deletions were found in a sample of over 6,000 controls. Expression analysis of Ctnna3 in the mouse cortex and hippocampus (P0-P90) provided support for its role in the early stage of brain development.

Conclusion

The finding of a rare compound heterozygous CTNNA3 exonic deletion segregating with ASD, the absence of CTNNA3 homozygous exonic deletions in controls and the high expression of Ctnna3 in both brain areas analysed implicate CTNNA3 in ASD susceptibility.

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Title: A CTNNA3 compound heterozygous deletion implicates a role for αT-catenin in susceptibility to autism spectrum disorder
Authors: Elena Bacchelli
Fabiola Ceroni
Dalila Pinto
Silvia Lomartire
Maila Giannandrea
Patrizia D'Adamo
Elena Bonora
Piero Parchi
Raffaella Tancredi
Agatino Battaglia
Elena Maestrini
Publication date: 01-12-2014
Publisher: BioMed Central
Published in: Journal of Neurodevelopmental Disorders / Issue 1/2014
Print ISSN: 1866-1947
Electronic ISSN: 1866-1955
DOI: https://doi.org/10.1186/1866-1955-6-17

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

A CTNNA3 compound heterozygous deletion implicates a role for αT-catenin in susceptibility to autism spectrum disorder

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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