Rosset Clévia, Vairo Filippo, Bandeira Isabel Cristina, Correia Rudinei Luis, de Goes Fernanda Veiga, da Silva Raquel Tavares Boy, Bueno Larissa Souza Mario, de Miranda Gomes Mireille Caroline Silva, Galvão Henrique de Campos Reis, Neri João I C F, Achatz Maria Isabel, Netto Cristina Brinckmann Oliveira, Ashton-Prolla Patricia
Laboratório de Medicina Genômica - Centro de Pesquisa Experimental - Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil.
Programa de pós-graduação em genética e biologia molecular, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
PLoS One. 2017 Oct 2;12(10):e0185713. doi: 10.1371/journal.pone.0185713. eCollection 2017.
Tuberous sclerosis complex (TSC) is an autosomal dominant multisystem disorder characterized by the development of multiple hamartomas in many organs and tissues. It occurs due to inactivating mutations in either of the two genes, TSC1 and TSC2, following a second hit in a tumor suppressor gene in most hamartomas. Comprehensive screening for mutations in both the TSC1 and TSC2 loci has been performed in several cohorts of patients and a broad spectrum of pathogenic mutations have been described. In Brazil, there is no data regarding incidence and prevalence of tuberous sclerosis and mutations in TSC1 and TSC2. We analyzed both genes in 53 patients with high suspicion of tuberous sclerosis using multiplex-ligation dependent probe amplification and a customized next generation sequencing panel. Confirmation of all variants was done by the Sanger method. We identified 50 distinct variants in 47 (89%) of the patients. Five were large rearrangements and 45 were point mutations. The symptoms presented by our series of patients were not different between male and female individuals, except for the more common occurrence of shagreen patch in women (p = 0.028). In our series, consistent with other studies, TSC2 mutations were associated with a more severe phenotypic spectrum than TSC1 mutations. This is the first study that sought to characterize the molecular spectrum of Brazilian individuals with tuberous sclerosis.
结节性硬化症（TSC）是一种常染色体显性多系统疾病，其特征是在许多器官和组织中出现多个错构瘤。它是由于两个基因TSC1和TSC2中的任何一个发生失活突变所致，在大多数错构瘤中，肿瘤抑制基因发生第二次打击后就会出现这种情况。已经在几组患者中对TSC1和TSC2基因座的突变进行了全面筛查，并描述了广泛的致病突变。在巴西，没有关于结节性硬化症的发病率和患病率以及TSC1和TSC2突变的数据。我们使用多重连接依赖探针扩增和定制的下一代测序面板分析了53例高度怀疑患有结节性硬化症的患者的这两个基因。所有变异均通过桑格法进行确认。我们在47名（89%）患者中鉴定出50种不同的变异。其中5种是大片段重排，45种是点突变。除了女性更常见鲨革斑外（p = 0.028），我们系列患者出现的症状在男性和女性个体之间没有差异。在我们的系列中，与其他研究一致，TSC2突变比TSC1突变与更严重的表型谱相关。这是第一项旨在描述巴西结节性硬化症患者分子谱的研究。
