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INTS11-related neurodevelopmental disorder: a case report and literature review

Journal of Human Genetics (2024)Cite this article

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Abstract

Background

INTS11 is a critical catalytic component of the Integrator complex that regulates RNA polymerase II termination and modulates gene expression. Until recently, INTS11 mutations were associated with human neurodevelopmental disorders, characterized by global developmental and language delays, generalized hypotonia, and progressive brain atrophy.

Case

We report the case of a 2-year-old Chinese girl who presented with global developmental delay, generalized hypotonia, refractory epilepsy, craniofacial dysmorphism, and progressive brain atrophy. Novel variants were identified in exon 2 of INTS11 gene c.588_589del (p. Trp197AspfsTer2) and c.457_459del (p. Glu153del).

Conclusion

We identified a compound heterozygous mutation in INTS11, a clinical feature consistent with two previous reports of the variants in human INTS11, but her recurrent seizures were more pronounced and refractory to most antiepileptic drugs and ketogenic diets.

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Acknowledgements

We wish to thank the patient and his family for participation in the study. We also thank the staffs of Chigene (Beijing) Translational Medical Research Center Co. Ltd. for providing next generation sequencing, analysing genetic diseases, and discussion.

Funding

This study was funded by STI 2030-Major Projects under Grant No. 2021ZD0201700.

Author information

Authors and Affiliations

  1. Department of Neurology, The Children’s Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, 310052, China

    Lihua Jiang, Yilong Wang, Weiqin Zhang, Xin Zhang, Feng Gao & Zhefeng Yuan

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  1. Lihua Jiang
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  2. Yilong Wang
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  3. Weiqin Zhang
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  4. Xin Zhang
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  5. Feng Gao
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  6. Zhefeng Yuan
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Contributions

All authors contributed to the study conception and design. ZY, LJ and FG designed the research and performed the research; clinical data were collected by LJ, XZ and WZ. YW performed the bioinformatics analysis; LJ wrote and revised the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Zhefeng Yuan.

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Competing interests

The authors declare no competing interests.

Ethics approval and consent to participate

The studies involving human participants were reviewed and Approved by the Ethics Committee of Children’s Hospital, Zhejiang University School of Medicine (2021-IRB-161). The participants’ legal guardians/next of kin provided written informed consent to participate in this study.

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Jiang, L., Wang, Y., Zhang, W. et al. INTS11-related neurodevelopmental disorder: a case report and literature review. J Hum Genet (2024). https://doi.org/10.1038/s10038-024-01276-z

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  • DOI: https://doi.org/10.1038/s10038-024-01276-z

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