Relationship between gene mutation and clinical phenotype in patients with tuberous sclerosis complex / 中华神经科杂志

ABSTRACT

Objective To study the relationship between gene mutation and clinical phenotype in patients with tuberous sclerosis complex (TSC).Methods The clinical data of 76 patients with TSC diagnosed in Guangdong 999 Brain Hospital were collected between May 2007 and May 2014 and then TSC gene mutation analysis was performed.Genotype-phenotype analyses for all the patients were also carried out.Results Fifty of the 76 (66％) patients were male,and 26 (34％) were female,in which 19 (31％) patients presented with cyst-like cortical tuber,69 (92％) with skin lesions,16 (30％) with renal lesions,50 (69％) with mental retardation and 39 still suffered seizures after a year.In this study,22 (29％) cases showed TSC1 gene mutation,31 (59％) presented TSC2 gene mutation,and 15 (20％)cases had no mutation identified.The mutation ratio of TSC1 ∶ TSC2 was approximately 3 ∶ 5,while the mutation ratio of TSC1 ∶ TSC2 was 1 ∶ 1 for familial TSC patients,and 1 ∶ 2 for sporadic TSC patients.Comparing to those with TSC1 gene mutation and no mutation identified,patients with TSC2 gene mutation exhibited statistical meaning on the aspects of the onset age of seizure (Z =1.688,P =0.007),seizure onset before l-year-old (x2 =10.584,P =0.001),epilepsy duration (x2 =4.996,P =0.025),spasms onset (x2 =10.111,P =0.001),cyst-like cortical tuber (x2 =9.182,P =0.002),skin lesions (x2 =9.016,P =0.003),as well as renal lesions (x2 =6.079,P =0.014).No apparent relation was found between genotype and intelligence outcome.Conclusions The patients with TSC2 gene mutations presented severer symptoms in seizure onset than those with TSC1 gene mutation and no mutation identified.The patients with TSC2 gene mutation were characterized by early onset of seizure,especially before 1-year-old,others like spasms onset,cyst-like cortical tuber,skin lesions,as well as renal lesions being more vulnerable.Therefore,more active treatment should be given to the patients with TSC2 gene mutation.