Genotype-phenotype correlation between TSC1 and TSC2 associated tuberous sclerosis complex / 中华实用儿科临床杂志

ABSTRACT

Objective To investigate the genotype-phenotype correlation between TSC1 and TSC2 associated tuberous sclerosis complex(TSC).Methods Nineteen infants with TSC were enrolled in the study.Their clinical manifestations and mutations of TSC gene were analyzed by chip capturing and next-generation sequencing.Results Among the total of 19 patients with TSC,13 TSC2 mutations and 4 TSC1 mutations were detected.The ratio of TSC2/TSC1 mutation-positive cases was 3.4/1.Six mutations were novel.There were epilepsy in 10 cases carrying TSC2 mutations,including 4 cases (31％) with refractory to antiepileptic treatment,and 3 cases carrying TSC1 mutations,including 1 case (25 ％)with refractory to antiepileptic treatment.The incidence and severity (grade 2)of epilepsy,brain imaging were not different in TSC2 and TSC1 patients(P =0.480 7,0.462 2).Compared with clinical manifestations,incidence of mental retardation (grade 1 or grade 2) was higher in TSC2 patients (85 ％,11/13 cases) than TSC1 patients (50 ％,2/4 cases).Also,the incidence of moderate and severe mental retardation (grade 2) was higher in TSC2 patients (54％,7/13 cases) in comparison with TSC1 patients(25％,1/4 cases).Compared with the phenotype of TSC2 and TSC1 patients,the frequencies of skin,renal and cardiac lesions were significantly higher in TSC2 patients than TSC1 patients.Conclusions TSC2 mutation may be the prominent molecular pathogenesis in Han population with TSC.TSC2 patients have much profound muhisystemitc leisions than TSC1 patients,including mental retardation,epilepsy,facial angiofibromas and renal angiomyolipomas etc,which should be confirmed further in domestic multicenter and large samples.