| Tuberous sclerosis complex(TSC)is an autosomal dominant disorder characterized by hamartomas in the affected organs. It can affect several organs in the human body including the brain, heart, kidneys, eyes, skin and lungs. Clinical symptoms of TSC include epilepsy, mental retardation, autism, facial angiofibromas, renal angiomyolipomas, and pulmonary lymphangiomyomatosis. It was first described in depth by Bourneville in 1880. TSC affects both sexes and all ethnic groups. The prevalence is estimated to be one case per 6000 to 10,000 individuals. The disease is caused by inactivation of either the TSC1 gene on chromosome 9q34 or the TSC2 gene on chromosome 16p13.3. The genes TSC1 and TSC2 encode, respectively, proteins called hamartin and tuberin. To date, 211 TSC1 and 743 TSC2 unique variants have been reported, but the mutational hotspots have not been found. Meanwhile, the TSC displays genetic heterogeneity. So, the phenotypic expression of TSC is highly variable and in some case it can be difficult to establish a definitive clinical diagnosis.In this study, we collected a Chinese twins family with tuberous sclerosis complex and carried out molecular genetics research. By linkage analysis and direct DNA sequence analysis, we found a mutation in exon 19 of the TSC2 gene: c.2138G>A(p.A678T). This mutation is a de novo mutation and inactivates tuberin. We also found the same change in I1, II3, and II5 of the family, but they don't have any clinical feature. We think that it was nonpenetrance. Other people in the family were normal. Mutation analysis was carried out using restriction fragment length polymorphism ( RFLP ) in 200 unrelated population--matched controls, but 3 persons were found to have the same change. According to our research demonstration and results, we speculate that this mutation comes from agnate and the carriers don't have the disease or not be found for mild symptom. We think this mutation is the cause of the clinical phenotypes of the patients with TSC.
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