Clinical and molecular characterization of patients fulfilling Chompret criteria for Li-Fraumeni syndrome in Southern Brazil.

Li-Fraumeni syndrome (LFS) is an autosomal dominant cancer predisposition syndrome caused by pathogenic germline variants in the TP53 gene, characterized by a predisposition to the development of a broad spectrum of tumors at an early age. The core tumors related to LFS are bone and soft tissue sarcomas, premenopausal breast cancer, brain tumors, adrenocortical carcinomas (ACC), and leukemias. The revised Chompret criteria has been widely used to establish clinical suspicion and support TP53 germline variant testing and LFS diagnosis.

Tuberous Sclerosis Complex with rare associated findings in the gastrointestinal system: a case report and review of the literature.

Background: Tuberous Sclerosis Complex (TSC) is a complex and heterogeneous genetic disease that has well-established clinical diagnostic criteria. These criteria do not include gastrointestinal tumors.

Case Presentation: We report a 45-year-old patient with a clinical and molecular diagnosis of TSC and a family history of cancer, presenting two rare associated findings: gastrointestinal polyposis and pancreatic neuroendocrine tumor.

Haplotypic characterization of BRCA1 c.5266dupC, the prevailing mutation in Brazilian hereditary breast/ovarian cancer.

Specific pathogenic mutations associated with breast cancer development can vary between ethnical groups. One example is BRCA1 c.5266dupC that was first described as a founder mutation in the Ashkenazi Jewish population, but was later also found in other populations.

Synchronous Periampullary Tumors in a Patient With Pancreas Divisum and Neurofibromatosis Type 1.

Introduction: In this study, we describe for the first time a Neurofibromatosis type 1 patient with pancreas divisum, multiple periampullary tumors and germline pathogenic variants in and genes.

Case Report: A 62-year-old female NF1 patient presented with weakness, choluria, nausea, and diffuse abdominal pain to an emergency room service. Magnetic resonance imaging revealed an abdominal mass involving the periampullary region and pancreas divisum.

TP53 p.Arg337His germline mutation prevalence in Southern Brazil: Further evidence for mutation testing in young breast cancer patients.

Premenopausal breast cancer (BC) is a core tumor of Li-Fraumeni (LFS) and Li-Fraumeni-like (LFL) Syndromes, predisposition disorders caused by germline mutations in TP53 gene. In the Southern and Southeastern regions of Brazil, a specific TP53 germline mutation, c.1010G>A (p.

Screening and characterization of BRCA2 c.156_157insAlu in Brazil: Results from 1380 individuals from the South and Southeast.

Portuguese immigration to Brazil occurred in several waves and greatly contributed to the genetic composition of current Brazilian population. In this study, we evaluated the frequency of a Portuguese founder Alu insertion in BRCA2 exon 3 (c.156_157insAlu) among individuals fulfilling Hereditary Breast and Ovarian Cancer (HBOC) syndrome criteria in 1,380 unrelated families originated from three distinct Brazilian States.

The germline mutational landscape of BRCA1 and BRCA2 in Brazil.

The detection of germline mutations in BRCA1 and BRCA2 is essential to the formulation of clinical management strategies, and in Brazil, there is limited access to these services, mainly due to the costs/availability of genetic testing. Aiming at the identification of recurrent mutations that could be included in a low-cost mutation panel, used as a first screening approach, we compiled the testing reports of 649 probands with pathogenic/likely pathogenic variants referred to 28 public and private health care centers distributed across 11 Brazilian States. Overall, 126 and 103 distinct mutations were identified in BRCA1 and BRCA2, respectively.

Clinical and molecular characterization of neurofibromatosis in southern Brazil.

Objectives: Neurofibromatoses (type 1: NF1; type 2: NF2) are autosomal dominant tumor predisposition syndromes mostly caused by loss-of-function mutations in the tumor suppressor genes NF1 and NF2, respectively. Genotyping is important for correct diagnosis of these diseases. The authors aimed to characterize NF1 and NF2 variants in patients from Southern Brazil.

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

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.

TSC1 and TSC2 gene mutations and their implications for treatment in Tuberous Sclerosis Complex: a review.

Tuberous sclerosis complex is an autosomal dominant disorder characterized by skin manifestations and formation of multiple tumors in different organs, mainly in the central nervous system. Tuberous sclerosis is caused by the mutation of one of two tumor suppressor genes, TSC1 or TSC2. Currently, the development of novel techniques and great advances in high-throughput genetic analysis made mutation screening of the TSC1 and TSC2 genes more widely available.

Pediatric cancer and Li-Fraumeni/Li-Fraumeni-like syndromes: a review for the pediatrician.

Introduction: cancer is the second leading cause of death in children between the ages of 0 and 14 years, corresponding to approximately 3% of all cases diagnosed in Brazil. A significant percentage (5-10%) of pediatric cancers are associated with hereditary cancer syndromes, including Li-Fraumeni/Li-Fraumeni-like syndromes (LFS/LFL), both of which are caused by TP53 germline mutations. Recent studies have shown that a specific TP53 mutation, known as p.

DNA damage in Fabry patients: An investigation of oxidative damage and repair.

Fabry disease (FD) is a lysosomal storage disorder associated with loss of activity of the enzyme α-galactosidase A. In addition to accumulation of α-galactosidase A substrates, other mechanisms may be involved in FD pathophysiology, such as inflammation and oxidative stress. Higher levels of oxidative damage to proteins and lipids in Fabry patients were previously reported.

Knowledge about breast cancer and hereditary breast cancer among nurses in a public hospital.

Objective: To assess the knowledge of nurses involved in the care of oncology patients in a public university hospital, regarding breast cancer and hereditary breast cancer, and to verify the use of such knowledge in their daily practice.

Methods: This is a descriptive cross-sectional study. Data were obtained through a structured, self-administered questionnaire.

TP53 p.R337H is a conditional cancer-predisposing mutation: further evidence from a homozygous patient.

Background: Adrenocortical carcinomas (ACCs) are among the most common childhood cancers occurring in infants affected with the Li-Fraumeni and Li- Fraumeni-like (LFS/LFL) syndromes, which are caused by dominant germline mutations in the TP53 gene. In Brazil, a particular mutation, occurring in the tetramerisation domain of the gene, p.R337H, is exceedingly common due to a founder effect and is strongly associated with ACC.

Quality of life of brazilian patients with Gaucher disease and fabry disease.

Objective: To evaluate QoL in a sample of Brazilian patients with Gaucher (GD) and Fabry (FD) disease using the SF-36 survey.

Method: Observational cross-sectional study. The SF-36 survey was administered to cognitively able patients 12 years or older, who were seen in the Medical Genetics Service of Hospital de Clínicas de Porto Alegre, Brazil.

Increased oxidative damage in carriers of the germline TP53 p.R337H mutation.

Germline mutations in TP53 are the underlying defect of Li-Fraumeni Syndrome (LFS) and Li-Fraumeni-like (LFL) Syndrome, autosomal dominant disorders characterized by predisposition to multiple early onset cancers. In Brazil, a variant form of LFS/LFL is commonly detected because of the high prevalence of a founder mutation at codon 337 in TP53 (p.R337H).

Globotriaosylceramide is correlated with oxidative stress and inflammation in Fabry patients treated with enzyme replacement therapy.

Fabry disease is an X-linked inborn error of glycosphingolipid catabolism due to deficient activity of α-galactosidase A that leads to accumulation of the enzyme substrates, mainly globotriaosylceramide (Gb3), in body fluids and lysosomes of many cell types. Some pathophysiology hypotheses are intimately linked to reactive species production and inflammation, but until this moment there is no in vivo study about it. Hence, the aim of this study was to investigate oxidative stress parameters, pro-inflammatory cytokines and Gb3 levels in Fabry patients under treatment with enzyme replacement therapy (ERT) and finally to establish a possible relation between them.

Clinical aspects of neuropathic lysosomal storage disorders.

The purpose of this review is to describe neurological phenotypes associated with lysosomal storage diseases (LSDs), focusing on features arising from primary neuronal involvement. Clinical presentation, progression and genetic data, are discussed in detail in Part 2, the electronic material. Main features are summarized in Part 1.

Population prevalence of hereditary breast cancer phenotypes and implementation of a genetic cancer risk assessment program in southern Brazil.

In 2004, a population-based cohort (the Núcleo Mama Porto Alegre - NMPOA Cohort) was started in Porto Alegre, southern Brazil and within that cohort, a hereditary breast cancer study was initiated, aiming to determine the prevalence of hereditary breast cancer phenotypes and evaluate acceptance of a genetic cancer risk assessment (GCRA) program. Women from that cohort who reported a positive family history of cancer were referred to GCRA. Of the 9218 women enrolled, 1286 (13.

White matter lesions in Fabry disease before and after enzyme replacement therapy: a 2-year follow-up.

Purpose: To report the clinical and neuroimaging, central nervous system (CNS) findings of patients with Fabry disease (FD) during 24 months of enzyme replacement therapy (ERT) with agalsidase-alpha.

Method: Eight patients were included. Six completed 24 months of ERT.

Serum S100B protein is increased in fasting rats.

Background: S100B is a calcium-binding protein expressed and secreted by astrocytes; serum and cerebrospinal fluid (CSF) S100B elevation has been proposed as an index of brain damage. However, other tissues are shown to produce this protein and the clinical significance of serum S100B elevation has been discussed.

Methods: We investigated the levels of serum and CSF S100B in fasting Wistar rats.

Serum S100B levels in patients with neural tube defects.

Background: We investigated the levels of S100B protein in the serum of patients with neural tube defects (NTD), and the ontogenetic variation on this group of patients.

Methods: Samples from 24 control individuals and 25 patients with NTD were studied. S100B protein levels were determined using LIA-mat Sangtec kit.