Atypical genomic cortical patterning in autism with poor early language outcome

Published on May 20, 2021in bioRxiv
· DOI :10.1101/2020.08.18.253443
Michael V. Lombardo55
Estimated H-index: 55
(IIT: Istituto Italiano di Tecnologia),
Lisa T. Eyler47
Estimated H-index: 47
(UCSD: University of California, San Diego)
+ 13 AuthorsEric Courchesne116
Estimated H-index: 116
(UCSD: University of California, San Diego)
Cortical regionalization develops via genomic patterning along anterior-posterior (A-P) and dorsal-ventral (D-V) gradients. Here we find that normative A-P and D-V genomic patterning of cortical surface area (SA) and thickness (CT) present in typically developing and autistic toddlers with good early language outcome, is absent in autistic toddlers with poor early language outcome. Autistic toddlers with poor early language outcome are instead specifically characterized by secondary and independent genomic patterning effect on CT. Genes involved in these effects can be traced back to midgestational A-P and D-V gene expression gradients and different prenatal cell (e.g., progenitor cells, excitatory neurons), are functionally important for vocal learning and human-specific evolution, and are prominent in prenatal co-expression networks enriched for high-penetrance autism risk genes. Autism with poor early language outcome may be explained by atypical genomic cortical patterning starting in prenatal development, which may detrimentally impact later regional functional specialization and circuit formation.
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#1Michael V. Lombardo (IIT: Istituto Italiano di Tecnologia)H-Index: 55
#2Elena Maria Busuoli (IIT: Istituto Italiano di Tecnologia)
Last. Karen Pierce (UCSD: University of California, San Diego)H-Index: 51
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Early detection and intervention are believed to be key to facilitating better outcomes in children with autism, yet the impact of age at treatment start on outcome is poorly understood. While clinical traits such as language ability have been shown to predict treatment outcome, whether or not and how information at the genomic level can predict treatment outcome is unknown. Leveraging a cohort of toddlers with autism who all received the same standardized intervention at a very young age and pr...