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

• Published in: PloS one Vol. 12; no. 10; p. e0185713
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 02.10.2017; Public Library of Science (PLoS)
• Subjects: Biology and Life Sciences; Brazil; Brazilians; Cancer; Customization; Family; Female; Gene mutation; Genes; Genetic aspects; Genetic counseling; Genetic Predisposition to Disease; Genetics; Genomics; Health aspects; Hereditary diseases; High-Throughput Nucleotide Sequencing - methods; Humans; Male; Medical diagnosis; Medicine and Health Sciences; Multiplexing; Mutation; Organs; Patients; People and places; Phenotypes; Proteins; Research and Analysis Methods; Sequences; Tissues; Tuberous sclerosis; Tuberous Sclerosis - genetics; Tuberous Sclerosis Complex 1; Tuberous Sclerosis Complex 2; Tumor suppressor genes; Tumor Suppressor Proteins - genetics; Brazil; Rio Grande do Sul Brazil; Rio de Janeiro Brazil
• ISSN: 1932-6203; 1932-6203
• 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.