OBJECTIVETo identify pathogenic mutation of the TSC1 and TSC2 genes in a patient with tuberous sclerosis.

METHODSPeripheral venous blood samples and clinical data of a pregnant woman with tuberous sclerosis and 4 family members (parents, uncle and husband) were collected. Genomic DNA was extracted. All coding exons of the TSC1 and TSC2 genes and their flanking intronic sequences were amplified by polymerase chain reaction and subjected to direct sequencing.

RESULTSThe patient has presented facial angiofibroma and prefrons fibrous plaque for 20 years, and lumbar connective tissue nevus for 10 years. She also had mental retardation but no epilepsy. A novel frame-shift mutation c.4258-4261delTCAG was detected in exon 34 of the TSC2 gene, which had led to a premature stop codon TAG after the 55th amino acids. The same mutation was not found in the unaffected family members and 100 unrelated healthy controls.

CONCLUSIONThe novel frame-shifting mutation c.4258-4261delTCAG (p.Ser1420GlyfsX55) in the TSC2 gene may be responsible for the disease in the patient.

Adult ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; China ; DNA Mutational Analysis ; Female ; Humans ; Male ; Molecular Sequence Data ; Mutation ; Pedigree ; Pregnancy ; Tuberous Sclerosis ; genetics ; Tumor Suppressor Proteins ; genetics ; Young Adult

OBJECTIVETo identify pathogenic mutations of TSC1 and TSC2 genes in two familial and one sporadic cases with tuberous sclerosis complex (TSC).

METHODSFor five patients and their family members, potential mutations of the TSC1 and TSC2 genes were detected by direct sequencing.

RESULTSFor one family, a novel missense mutation c.1964C>T (p.S655F) was detected in the exon 19 of the TSC2 gene. For the sporadic patient, a repeat substitution with deletion mutation c.5238-5255delCATCAAGCGGCTCCGCCA (p.His1746GlnfsX56) was detected in the exon 40 of the TSC2 gene, which led to a stop codon TGA after the 56th amino acids. No mutation was found in another family.

CONCLUSIONThe missense mutation c.1964C>T(P.S655F) and the substitution with deletion mutation 5238-5255delCATCAAGCGGCTCCGCCA(p.His1746GlnfsX56) of the TSC2 gene probably underlie the disease in the first family and the sporadic case.

Adolescent ; Adult ; Base Sequence ; Child, Preschool ; DNA Mutational Analysis ; Female ; Humans ; Male ; Mutation, Missense ; Pedigree ; Phenotype ; Tuberous Sclerosis ; genetics ; Tumor Suppressor Proteins ; genetics