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Whole exome sequencing and transcriptome analysis in two unrelated patients with novel SET mutations

Journal of Human Genetics volume 68, pages 867–874 (2023)Cite this article

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Abstract

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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Fig. 1: Clinical characteristics of the two patients.
Fig. 2: Alternative splicing isoforms of the SET gene in patient 1.
Fig. 3: RT-qPCR of the SET gene in the patients
Fig. 4: Differentially expressed genes and enriched KEGG pathways
Fig. 5: Gene set enrichment analysis (GSEA) identifies dysregulated KEGG pathways in the patients.
Fig. 6: Summary of P/LP variants in the SET gene cause ID.

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Data availability

The datasets used and/or analyzed during the current study available from the corresponding author, (BT), on reasonable request.

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Acknowledgements

We appreciate the patients and their family members for their participation in this study.

Funding

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).

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Author notes

  1. These authors contributed equally: Xin Pan, Sihan Liu, Xiaoshu Feng.

Authors and Affiliations

  1. Department of Gynecology and Obstetrics, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China

    Xin Pan, Li Liu, Xu Zhang, Guanhua Qian, Hong Yao, Xiaojing Dong & Bo Tan

  2. Institute of Rare Diseases, West China Hospital of Sichuan University, Chengdu, China

    Sihan Liu & Xiaoshu Feng

  3. College of Computer Science, Chongqing University, Chongqing, China

    Na Liang

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Contributions

Conceptualization: XP, SL, XF and BT; Data curation: XP; Formal Analysis: SL, XF and BT; Funding acquisition: HY, XD and BT; Investigation: LL, ZX, GQ and NL; Project administration: HY, XD and BT, Supervision: HY, XD and BT; Visualization: SL, XF and BT; Writing – original draft: SL, XF and BT; Writing – review & editing: HY, XD and BT.

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Correspondence to Bo Tan.

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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

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