Molecular analysis of TSC1 and TSC2 genes and phenotypic correlations in Brazilian families with tuberous sclerosis

作者：Rosset Clevia; Vairo Filippo; Bandeira Isabel Cristina; Correia Rudinei Luis; de Goes Fernanda Veiga; Boy da Silva Raquel Tavares; Mario Bueno Larissa Souza; Silva de Miranda Gomes Mireille Caroline; Reis Galvao Henrique de Campos; Neri Joao I C F; Achatz Maria Isabel; Oliveira Netto Cristina Brinckmann; Ashton Prolla Patricia^*

来源：PLos One, 2017, 12(10): e0185713.

DOI：10.1371/journal.pone.0185713

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.

• 出版日期2017-10-2