Identification of TSC2 mosaic mutation limited to cortical tuber with TSC targeted sequencing: a case report and literature review



Tuberous sclerosis complex (TSC) is an autosomal dominant disorder, mainly in childhood presents epilepsy due to cortical tubers. TSC1/TSC2 pathogenic variants cannot be detected in regular molecular genetic testing in around 10-15% of TSC patients.


We analyzed TSC genes in both cortical tuber, blood and skin samples from a pediatric patient with refractory epilepsy.


We found no germline mutations by whole-exome sequencing. Well in targeted sequencing of TSC1/2 data, we identified de novo mutations only in cortical tuber: TSC2 NM_000548.5: exon34:c.4183C>T (p.Gln1395*) in 3% of the alleles. No other TSC mutations were found in patient’s blood and skin samples and her parents’ blood sample.


Our case report found TSC2 mosaic mutations can be only limited to cortical tuber in patients with TSC.

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Tuberous sclerosis complex


Next generation sequencing


No mutations identified


Whole-exome sequencing


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We would like to thank to patient and family who contributed to this study. We also thank Lei Liu for his assistance in genetic analysis.

Availability of data and materials

The hg38/GRCh38 human reference genome ( was used as the reference dataset in this study. The reference sequence used for the validation of the c.4183C>T (p.Gln1395*) variant in TSC2 was obtained from NCBI Nucleotide using the accession number NM_000548.5. The variation is available in the Clinvar and HGMD PRO database, with accession ID: VCV000280596 and CM174666 respectively.


This study was supported by Research Project of Shanghai Municipal Health Commission (201940351) and the science and technology commission of Shanghai (18411962000). The funding bodies played no direct role in the design of the study, the collection, analysis, or interpretation of data, or the writing of the manuscript. The cost of sequencing was borne by the two funding projects.

Author information




YFZ is the first author and performed data analysis and interpretation, and drafted the manuscript. XHW, JW, and YFD performed interpretation of clinical data. HL and YW conceived the idea for the study and supervised the study. BBW and RZH are the corresponding authors and conceived the idea for the study, designed the experiments, responsible for the analysis and interpretation of sequencing data, and drafted and revised the manuscript content. All authors participated in the proofreading. The authors have read and approved the final manuscript.

Corresponding authors

Correspondence to Rui Zhao or Bingbing Wu.

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Ethics approval

The local ethics committee of Children’s Hospital of Fudan University approved the study protocol.

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Parents gave written informed consent for study participation

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Written informed consent for publication for identifying images or other personal or clinical details was obtained from both the patient’s parents.

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The authors declare that they have no competing interests.

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Zhou, Y., Wang, X., Wang, J. et al. Identification of TSC2 mosaic mutation limited to cortical tuber with TSC targeted sequencing: a case report and literature review. Childs Nerv Syst (2021).

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  • Tuberous sclerosis complex
  • Cortical tuber
  • TSC2
  • Targeted sequencing