Germline mutation of TSC1 or TSC2 gene in Chinese patients with bilateral renal angiomyolipomas and mutation spectrum of Chinese TSC patients

The germline mutation of the TSC1/2 gene in bilateral renal angiomyolipomas is unclear. Meanwhile, the mutation spectrum of Chinese TSC patients has not been revealed. We recruited 78 patients diagnosed with bilateral renal AMLs. High-throughput sequencing was used to detect any variants in TSC1/2 genes. The results showed that 28.6% of patients diagnosed before 45 were with positive results of TSC1/2 test. The rate decreased to 14.3% for those with onset age over 45. For the 315 previously reported Chinese patients, TSC1 patients were more likely to be affected by nonsense mutations (51.1% vs. 20.7%, p<0.001) and had a significantly higher rate of family history than TSC2 patients (37.8% vs. 19.6%, p=0.0067). Moreover, exon8, 15, and 18 were the hotspot mutation regions for TSC1, and exon 29, 33 and 40 were the most common mutation regions for TSC2. Besides, Chinese TSC patients carried more TSC2 alterations (85.7% vs.76.2%, p<0.001), and were more likely to have a family history than those from TOSCA (22.2% vs. 13.9%, p<0.001). In conclusion, patients affected by bilateral renal AMLs should receive genetic testing of TSC 1/2 genes and Chinese TSC patients have relatively hotspot mutation regions, which are helpful to genetic counseling and clinical decision making.