[Genetic analysis of a mosaic case with low proportion mutation of TSC2 gene]

To perform gene mutation analysis in a patient with atypical clinical manifestations of tuberous sclerosis (TSC) for definite diagnosis.

Peripheral blood DNA was obtained from a patient with clinically suspected TSC and her parents, and all exons and their flanking sequences of TSC1 and TSC2 genes in the proband were sequenced by whole exome sequencing to determine the candidate pathogenic mutations. At the same time, Sanger sequencing was performed to verify the peripheral blood DNA of the patient and her parents. And the mosaic percentage of the mutation in the proband's somatic cells was detected by the droplet digital PCR method.

A heterozygous nonsense mutation c.1096G>T (p.E366*) was identified in the exon 11 of the TSC2 gene, which only had a small mutation peak. A lower percentage of the mutation was found in the DNA of the patient than that in the public database, therefore the possibility of mosaicism might not be excluded. In addition, the droplet digital PCR method demonstrated that the proband was a c.1096G>T mutant mosaicism, and the mosaic percentage was 14%.

The somatic mosaic mutation c.1096G>T (p.e366*) may be responsible for the phenotype of TSC in this patient. And the drop digital PCR is expected to be a diagnostic method for somatic cells mosaicism.