Genetic analysis of a pedigree affected with tuberous sclerosis complex caused by a novel mutation of TSC1 / 中华医学遗传学杂志

Objective@#To analyze the clinical phenotype of a Chinese pedigree affected with Tuberous sclerosis complex(TSC) and explore pathogenic mutations of TSC1 and TSC2 gene.@*Methods@#Unique clinical phenotypes, the results of imaging, examination of the proband and special family history, collectively, made the constellation of features of TSC.Genomic DNA was obtained from six affected and eight unaffected members of the family and potential mutations of the TSC1 and TSC2 genes were detected by PCR-amplification of the exons and exon-intron boundaries and direct sequencing.A total of 150 normal unrelated individuals were used as controls.@*Results@#Genetic analysis documented the presence of a heterozygous mutation, c. 1781_1782delTG (p.Val594GlyfsX11), in the exon 15 of TSC1 gene within all the patients of the family. This mutation was not observed in the eight unaffected family members or in the 150 unrelated control subjects from the same population , or the Human Gene Mutation Database(HGMD)and had completely co-segregated with the disease phenotype in the family.@*Conclusions@#The c. 1781_1782delTG mutation of TSC1 gene may be responsible for the tuberous sclerosis complex in this family. The data presented in the present study are of significance to clinicians, as well as genetic counselors, and may provide new clues for molecular diagnosis of this disease.

A sporadic case of tuberous sclerosis complex caused by a newly found heterozygous missense mutation of c.T1967C in TSC1 gene / 上海交通大学学报（医学版）

This paper reported a sporadic case of a 29-year-old Han female diagnosed with tuberous sclerosis complex (TSC) by next generation sequencing (NGS),one of genetic analysis techniques.She was admitted because of recurrent intractable seizure for 26 years,dizziness and headache for 3 months.Physical examination revealed angiofibromas over her face,shagreen patches in her lower back area,and hypomelanotic macules around her limbs and body.Cranial MRI manifested lesions on lateral ventricles,cerebellar vermis and left temporal lobe with abnormal signal changes on both sides of extensive cerebral cortex.A pathogenic and heterozygous missense mutation,c.T1967C,in exon 16 of her TSC1 gene was found via genetic tests,which has not yet been reported before.

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

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.