235 Genotype/phenotype correlations in 125 Chinese patients with tuberous sclerosis: a 29 years’ experience in hong kong

Background Tuberous Sclerosis Complex (TSC) is a multisystemic neurocutaneous disorder of autosomal dominant inheritance, with characteristic presentation of benign hamartomatous lesions across the brain, kidney, heart, eyes, skin and lungs. Objectives To study the mutation spectrum and phenotypic characteristics of TSC patients in the Chinese population, as well as to delineate the underlying genotype-phenotype correlations and compare with previous studies. Methods 120 patients suspected of TSC were referred to the Clinical Genetic Service (CGS), Department of Health, HKSAR for evaluation between 9/1991 and 8/2020. Blood samples from 105 patients presented with ≥1 major/ ≥2 minor diagnostic features according to the latest diagnostic criteria [1,2] are taken. Comprehensive genetic testing including sequencing and Multi-ligand probe-dependent Amplification (MLPA) was performed. Family screening was performed on molecularly confirmed cases. In total, 133 patients had a definite diagnosis, in which the 125 Chinese patients are included into the study. Statistical analyses (Pearson χ2 tests, Fisher exact test and ANOVA) are performed using SPSS version 26.0. Results Pathogenic genetic alternations are identified in 72.0% patients (90/125), in which 26.4% (33/125) have TSC1 and 45.6% (57/125) have TSC2 mutations. 28 novel mutations are reported while familial cases account for 23.2% (29/125). Males have significantly more subependymal nodules (47/55 vs 34/50; p=0.033) than females, whereas de novo cases have more cortical tubers (69/82 vs 14/24; p=0.007) and renal angiomyolipoma (44/85 vs 3/21; p=0.002) than familial cases. TSC2 cases have more frequent mental retardation (29/42 vs 4/25; p Conclusions The overall phenotypic spectrum and genotype-phenotype correlations in our Chinese cohort are compatible with literature. 28 novel mutations have been reported in this study.