Abstract
Purpose
Tuberous sclerosis complex (TSC) is an autosomal dominant multisystem disorder characterized by hamartomas in multiple organ systems. The TSC1 and TSC2 genes have been identified as the genetic basis of TSC. Two gene tests were used for definitive genetic diagnosis.
Methods
In our study, the case of a Chinese pediatric patient with seizures, hypomelanotic macules, hyperpigmented patches, multiple parenchymal lesions in the ventricle, and developmental retardation is detailed. Whole-genome sequencing (WGS) and multiplex ligation-dependent probe amplification (MLPA) were employed to detect genetic variations and copy number variations of TSC1 and TSC2.
Results
A novel heterozygous nonsense mutation in the TSC2 gene (c.3751A>T, p.Lys1251Ter) was identified in a Chinese pediatric patient suffering from TSC, whose unaffected parents did not carry this mutation. The mutation was classified as “pathogenic” according to the American College of Medical Genetics (ACMG) guidelines.
Conclusion
WGS was carried out to definitively diagnose and detect variations in the exon and noncoding region of the gene and copy number variations in the whole genome simultaneously. For diseases with complex genetic mechanisms, WGS as the first-line test can be efficient and cost-effective for clinical diagnosis.
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This work was supported by a grant from the National Natural Science Foundation of China (No. 81971219).
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This study was approved by the Ethics Committee of Xinqiao Hospital. Informed consent to this study was obtained from the parents of the patient.
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Yang, Mh., Wang, Zk., Huang, Y. et al. A novel de novo TSC2 nonsense mutation detected in a pediatric patient with tuberous sclerosis complex. Childs Nerv Syst 37, 253–257 (2021). https://doi.org/10.1007/s00381-020-04702-7
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DOI: https://doi.org/10.1007/s00381-020-04702-7