Brief Report: SETD2 Mutation in a Child with Autism, Intellectual Disabilities and Epilepsy
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Whole exome sequencing (WES) has been utilized with increasing frequency to identify mutations underlying rare diseases. Autism spectrum disorders (ASD) and intellectual disability (ID) are genetically heterogeneous, and novel genes for these disorders are rapidly being identified, making these disorders ideal candidates for WES. Here we report a 17-year-old girl with ASD, developmental delay, ID, seizures, Chiari I malformation, macrocephaly, and short stature. She was found by WES to have a de novo c.2028delT (P677LfsX19) mutation in the SET domain-containing protein 2 (SETD2) gene, predicted to be gene-damaging. This case offers evidence for the potential the role of SETD2 in ASD and ID and provides further detail about the phenotypic manifestations of mutations in SETD2.
KeywordsAutism spectrum disorder Autism SETD2 Intellectual disability Whole exome sequencing
We thank the patient and her family for their contribution. This work was supported in part by NIH Grant 5 T35 DK 93430-2.
Conflict of interest
No potential conflict of interest was disclosed.
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 (5). Informed consent was obtained from all patients for being included in the study. Additional informed consent was obtained from all patients for whom identifying information is included in this article.
- Carrozza, M. J., Li, B., Florens, L., Suganuma, T., Swanson, S. K., Lee, K. K., et al. (2005). Histone H3 methylation by Set2 directs deacetylation of coding regions by Rpd3S to suppress spurious intragenic transcription. Cell, 123(4), 581–592. doi: 10.1016/j.cell.2005.10.023.CrossRefPubMedGoogle Scholar
- Carvalho, S., Raposo, A. C., Martins, F. B., Grosso, A. R., Sridhara, S. C., Rino, J., et al. (2013). Histone methyltransferase SETD2 coordinates FACT recruitment with nucleosome dynamics during transcription. Nucleic Acids Research, 41(5), 2881–2893. doi: 10.1093/nar/gks1472.PubMedCentralCrossRefPubMedGoogle Scholar
- Hoyer, J., Ekici, A. B., Endele, S., Popp, B., Zweier, C., Wiesener, A., et al. (2012). Haploinsufficiency of ARID1B, a member of the SWI/SNF-a chromatin-remodeling complex, is a frequent cause of intellectual disability. American Journal of Human Genetics, 90(3), 565–572. doi: 10.1016/j.ajhg.2012.02.007.PubMedCentralCrossRefPubMedGoogle Scholar
- Sanders, S. J., Ercan-Sencicek, A. G., Hus, V., Luo, R., Murtha, M. T., Moreno-De-Luca, D., et al. (2011). Multiple recurrent de novo CNVs, including duplications of the 7q11.23 Williams syndrome region, are strongly associated with autism. Neuron, 70(5), 863–885. doi: 10.1016/j.neuron.2011.05.002.PubMedCentralCrossRefPubMedGoogle Scholar