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. 2021 Jul;71(7):1368-1377.
doi: 10.1007/s12031-020-01783-6. Epub 2021 Jan 22.

Alteration of TRIM33 Expression at Transcriptional and Translational Levels is Correlated with Autism Symptoms

Sattar Norouzi Ofogh  1 , Homa Rasoolijazi  2   3   4 , Esmaeil Shahsavand Ananloo  5   6 , Zahra Shahrivar  7 , Mohammad Taghi Joghataei  8   9   10 , Bahman Sadeghi  11 , Ali Bozorgmehr  12 , Fatemeh Alizadeh  13
Affiliations

Alteration of TRIM33 Expression at Transcriptional and Translational Levels is Correlated with Autism Symptoms

Sattar Norouzi Ofogh et al. J Mol Neurosci. 2021 Jul.

Abstract

As a complex neurodevelopmental disorder, autism affects children in three major cognitive domains including social interactions, language learning and repetitive stereotyped behaviors. Abnormal regulation of cell proliferation in the brain during the embryonic period via the TGF-β signaling pathway and TRIM33 gene that encodes a protein with a corepressor and regulatory role in this pathway has been considered as an etiology for autism. Here, we investigated the association of a variation of TRIM33 with autism symptoms at levels of mRNA and protein expression. We used Autism Diagnostic Interview-Revised (ADI-R) and Childhood Autism Rating Scale (CARS) as behavioral diagnostic tools. Normal and autistic children were genotyped for a TRIM33 polymorphism (rs11102807), and then expression was assessed at transcriptional and translational levels. Results demonstrated that the frequency of the homozygous A allele (AA genotype of rs11102807) was significantly higher in children with autism (P < 0.001), whereas carriers of the G allele were mostly among healthy individuals. Children homozygous for the rs11102807 A allele were associated with an increase in CARS and ADI-R scores, indicating a significant correlation with autism symptoms. TRIM33 gene expression at both mRNA (P < 0.01) and protein (P < 0.001) levels was significantly higher in controls compared to autistic children. A remarkable association between higher TRIM33 gene expression at the transcriptional level and lower scores for both CARS and ADI-R was observed in non-autistic children. It seems that rs11102807 modulates the function and expression of the TRIM33 gene, implying that the A allele may increase the risk of autism in children by reducing gene expression and altering the TGF-β signaling pathway.

Keywords: Autism; Autism Diagnostic Interview-Revised (ADI-R); Childhood Autism Rating Scale (CARS); TRIM33 gene polymorphism; Western blot.

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