RNA sequencing of blood from sex- and age-matched discordant siblings supports immune and transcriptional dysregulation in autism spectrum disorder.

Autor: Tomaiuolo P; Mafalda Luce Center for Pervasive Developmental Disorders, Milan, Italy., Piras IS; Neurogenomics Division, The Translational Genomics Research Institute, Phoenix, AZ, USA., Sain SB; Center for Translational Genomics and Bioinformatics, IRCCS San Raffaele Scientific Institute, Milan, Italy., Picinelli C; Mafalda Luce Center for Pervasive Developmental Disorders, Milan, Italy., Baccarin M; Mafalda Luce Center for Pervasive Developmental Disorders, Milan, Italy.; Department of Genetics, Synlab Suisse SA, Bioggio, Switzerland., Castronovo P; Mafalda Luce Center for Pervasive Developmental Disorders, Milan, Italy., Morelli MJ; Center for Translational Genomics and Bioinformatics, IRCCS San Raffaele Scientific Institute, Milan, Italy., Lazarevic D; Center for Translational Genomics and Bioinformatics, IRCCS San Raffaele Scientific Institute, Milan, Italy., Scattoni ML; Research Coordination and Support Service, Istituto Superiore di Sanità, Rome, Italy., Tonon G; Center for Translational Genomics and Bioinformatics, IRCCS San Raffaele Scientific Institute, Milan, Italy., Persico AM; Child and Adolescent Neuropsychiatry Program, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Via Giuseppe Campi 287, 41125, Modena, Italy. antonio.persico@unimore.it.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2023 Jan 16; Vol. 13 (1), pp. 807. Date of Electronic Publication: 2023 Jan 16.
DOI: 10.1038/s41598-023-27378-w
Abstrakt: Autism spectrum disorder (ASD) is a neurodevelopmental condition with onset in early childhood, still diagnosed only through clinical observation due to the lack of laboratory biomarkers. Early detection strategies would be especially useful in screening high-risk newborn siblings of children already diagnosed with ASD. We performed RNA sequencing on peripheral blood, comparing 27 pairs of ASD children vs their sex- and age-matched unaffected siblings. Differential gene expression profiling, performed applying an unpaired model found two immune genes, EGR1 and IGKV3D-15, significantly upregulated in ASD patients (both p adj = 0.037). Weighted gene correlation network analysis identified 18 co-expressed modules. One of these modules was downregulated among autistic individuals (p = 0.035) and a ROC curve using its eigengene values yielded an AUC of 0.62. Genes in this module are primarily involved in transcriptional control and its hub gene, RACK1, encodes for a signaling protein critical for neurodevelopment and innate immunity, whose expression is influenced by various hormones and known "endocrine disruptors". These results indicate that transcriptomic biomarkers can contribute to the sensitivity of an intra-familial multimarker panel for ASD and provide further evidence that neurodevelopment, innate immunity and transcriptional regulation are key to ASD pathogenesis.
(© 2023. The Author(s).)
Databáze: MEDLINE
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