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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/170559
Involvement of the 14-3-3 gene family in autism spectrum disorder and schizophrenia: Genetics, transcriptomics and functional analyses
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The 14-3-3 protein family are molecular chaperones involved in several biological functions and neurological diseases. We previously pinpointed YWHAZ (encoding 14-3-3ζ) as a candidate gene for autism spectrum disorder (ASD) through a whole-exome sequencing study, which identified a frameshift variant within the gene (c.659-660insT, p.L220Ffs*18). Here, we explored the contribution of the seven human 14-3-3 family members in ASD and other psychiatric disorders by investigating the: (i) functional impact of the 14-3-3ζ mutation p.L220Ffs*18 by assessing solubility, target binding and dimerization; (ii) contribution of common risk variants in 14-3-3 genes to ASD and additional psychiatric disorders; (iii) burden of rare variants in ASD and schizophrenia; and iv) 14-3-3 gene expression using ASD and schizophrenia transcriptomic data. We found that the mutant 14-3-3ζ protein had decreased solubility and lost its ability to form heterodimers and bind to its target tyrosine hydroxylase. Gene-based analyses using publicly available datasets revealed that common variants in YWHAE contribute to schizophrenia (p = 6.6 × 10-7), whereas ultra-rare variants were found enriched in ASD across the 14-3-3 genes (p = 0.017) and in schizophrenia for YWHAZ (meta-p = 0.017). Furthermore, expression of 14-3-3 genes was altered in post-mortem brains of ASD and schizophrenia patients. Our study supports a role for the 14-3-3 family in ASD and schizophrenia.
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TORRICO AVILÉS, Bàrbara, ANTÓN GALINDO, Ester, FERNÀNDEZ CASTILLO, Noèlia, ROJO FRANCÀS, Eva, GHORBANI, Sadaf, PINEDA CIRERA, Laura, HERVÁS, Amaia, RUEDA, Isabel, MORENO GUILLÉN, Estefanía, FULLERTON, Janice m., CASADÓ, Vicent, BUITELAAR, Jan k., ROMMELSE, Nanda, FRANKE, Barbara, REIF, Andreas, CHIOCCHETTI, Andreas g., FREITAG, Christine, KLEPPE, Rune, HAAVIK, Jan, TOMA, Claudio, CORMAND RIFÀ, Bru. Involvement of the 14-3-3 gene family in autism spectrum disorder and schizophrenia: Genetics, transcriptomics and functional analyses. _Journal of Clinical Medicine_. 2020. Vol. 9, núm. 6, pàgs. 1851. [consulta: 20 de gener de 2026]. ISSN: 2077-0383. [Disponible a: https://hdl.handle.net/2445/170559]