A Chinese tuberous sclerosis complex family and a novel tuberous sclerosis complex-2 mutation.

Tuberous sclerosis complex (TSC) is a relatively common autosomal dominant genetic disorder affecting 1/14,000–1/6000 Western populations. The incidence of TSC in Chinese population is still unknown although case reports of Chinese TSC patients were documented. The main clinical features of TSC include seizures, mental retardation, and the development of hamartomas in multiple organs such as the skin, brain, lung, heart, and kidney. Indeed, the disease virtually manifests in every organ. Two causative genes for TSC, TSC1 gene on chromosome 9q34 and TSC2 gene on chromosome16p13, have been identified in 1997 and 1993 respectively. Approximately, 70% of cases of TSC are de novo mutations. [3] Chinese TSC patients are more likely to have TSC2 missense and frame shift mutations. Here, we record one Chinese TSC family and it is novel frame shift mutation of TSC2. One TSC family was identified through a proband from Sichuan province of China. The proband, a 16‑year‑old male, first presented with frequent focal motor seizures at age of 6 years and was clinically diagnosed as TSC at age of 9 years. Physical examination found forehead fibrous plaque, facial angiofibromas [Figure 1a], hypopigmented macules, and shagreen patches on his back. [Figure 1b]. He has shown moderate mental retardation and failed to pass any academic examinations. Electroencephalogram (EEG) revealed multifocal spike wave and spike‑slow wave complex discharges. Cardiac ultrasound was normal, but renal ultrasound detected multiple small nodular hamartomas. His seizure was successfully controlled by sodium valproate and oxcarbazepine. The father of the proband is 48‑years‑old without epilepsy or mental retardation. However, physical examination revealed facial angiofibromas, shagreen patches on his back, and confetti‑like hypopigmented patches on his legs. Renal ultrasound revealed multiple hamartomas obviously larger than the proband. The third patient of the family was the younger brother of the proband. He was born when the proband was 11‑year‑old without any prenatal molecular diagnosis. At the age of 1 month, he began to experience frequent focal motor seizures, which could not be controlled by the combined treatment of sodium valproate, oxcarbazepine and topiramate, and demonstrated severe mental retardation. Physical examination was almost the same as the proband. EEG revealed focal and generalized epileptiform discharges. Multiple cardiac rhabdomyoma [Figure 1c] and nodular renal hamartomas were identified by ultrasound. In all the three patients, brain computed tomography showed multiple subependymal calcifications [Figure 1d] and brain magnetic resonance imaging detected multiple cortical tubers as well as subependymal nodules along the …