<i>TP53</i> p.R337H mutation carrier’s haplotypes.

<p>Shared haplotypes are highlighted in bold.</p><p><i>TP53</i> p.R337H mutation carrier’s haplotypes.</p

Age estimation for the p.Arg337His mutation as assessed by DMLE+2.3.

<p>Green lines show 95% CIs.</p

Average Pairwise Differences Among Haplotypes.

<p>Average Pairwise Differences Among Haplotypes.</p

Short Tandem Repeats position used for haplotype analysis and their respective position in chromosome 17p.

<p>Short Tandem Repeats position used for haplotype analysis and their respective position in chromosome 17p.</p

Primers and Short Tandem Repeats genomic position.

<p>Primers and Short Tandem Repeats genomic position.</p

Families with a likely benign or variant of uncertain significance in <i>TSC1</i> and <i>TSC</i>.

<p>Families with a likely benign or variant of uncertain significance in <i>TSC1</i> and <i>TSC</i>.</p

Molecular analysis of <i>TSC1</i> and <i>TSC2</i> genes and phenotypic correlations in Brazilian families with tuberous sclerosis

<div><p>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, <i>TSC1</i> and <i>TSC2</i>, following a second hit in a tumor suppressor gene in most hamartomas. Comprehensive screening for mutations in both the <i>TSC1</i> and <i>TSC2</i> 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 <i>TSC1</i> and <i>TSC2</i>. 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, <i>TSC2</i> mutations were associated with a more severe phenotypic spectrum than <i>TSC1</i> mutations. This is the first study that sought to characterize the molecular spectrum of Brazilian individuals with tuberous sclerosis.</p></div

Phenotypic comparison between male and female individuals with TSC.

<p>Phenotypic comparison between male and female individuals with TSC.</p