The human SET nuclear proto-oncogene (SET) gene is a protein-coding gene that encodes proteins that affects chromatin remodeling and gene transcription. Mutations in the SET gene have been reported to cause intellectual disability (ID) and epilepsy. In this study, we collected and analyzed clinical, genetic, and transcript features of two unrelated Chinese patients with ID. Both patients were characterized by moderate intellectual disability. Whole-exome sequencing identified two novel heterozygous mutations in the SET gene: NM_001122821.1:c.532-3 T > A and NM_001122821.1:c.3 G > C (p.0?). Additionally, RNA sequencing revealed widespread dysregulation of genes involved in NF-kB signaling and neuronal system in these two patients. To our knowledge, this is the first report of SET mutations causing ID in the Chinese population, broadening the genetic and ethnic spectrum of SET-related disorders and highlighting the importance of screening for SET gene variants.
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The datasets used and/or analyzed during the current study available from the corresponding author, (BT), on reasonable request.
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We appreciate the patients and their family members for their participation in this study.
This work was supported by the Scientific and Technological Research Program of Chongqing Municipal Education Commission (Grant No. KJQN202200420), Nan’an District Science and Health Joint Medical Scientific Research Project (2020-01), Program for Youth Innovation in Future Medicine, Chongqing Medical University (W0122), and Maternal and Child Health Research Cultivation Project of the Chongqing Health Commission (2023FY201).
The authors declare no competing interests.
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Pan, X., Liu, S., Feng, X. et al. Whole exome sequencing and transcriptome analysis in two unrelated patients with novel SET mutations. J Hum Genet 68, 867–874 (2023). https://doi.org/10.1038/s10038-023-01196-4