From abortion-inducing medications to Zika Virus Syndrome: 27 years experience of the First Teratogen Information Service in Latin America
In conclusion, SIAT is still evolving, as is the Medical Genetics Service that hosts it. Through its 27 years of existence more than 300 undergraduate and graduate students have rotated at SIAT. Presently, SIAT is expanding the research to experimental teratogenesis and to investigation of molecular mechanisms of teratogens. (Source: Genetics and Molecular Biology)
Source: Genetics and Molecular Biology - July 16, 2019 Category: Genetics & Stem Cells Source Type: research
The natural history of pregnancies with prenatal diagnosis of Trisomy 18 or Trisomy 13: Retrospective cases of a 23-year experience in a Brazilian public hospital
This study describes the overall outcome in a country where the therapeutic interruption of pregnancy is not available. The medical records of women with prenatal diagnosis of full trisomy of T13 or T18 between October 1994 and October 2017 were analyzed in order to describe their natural outcomes. Thirteen cases of T13 and 29 cases of T18 were included. The miscarriage rate was 9% for T18 and no cases for T13. Intrauterine fetal death occurred in 46% and 52% of cases for T13 and T18, respectively. The rate of live births for T13 was 54%, and the median survival was one day (95% CI -33.55 - 90.40) and 71% died in the first...
Source: Genetics and Molecular Biology - July 16, 2019 Category: Genetics & Stem Cells Source Type: research
Effects of gene therapy on cardiovascular symptoms of lysosomal storage diseases
Abstract Lysosomal storage diseases (LSDs) are inherited conditions caused by impaired lysosomal function and consequent substrate storage, leading to a range of clinical manifestations, including cardiovascular disease. This may lead to significant symptoms and even cardiac failure, which is an important cause of death among patients. Currently available treatments do not completely correct cardiac involvement in the LSDs. Gene therapy has been tested as a therapeutic alternative with promising results for the heart disease. In this review, we present the results of different approaches of gene therapy for LSDs, mainly in...
Source: Genetics and Molecular Biology - July 16, 2019 Category: Genetics & Stem Cells Source Type: research
Cyclic pamidronate treatment for osteogenesis imperfecta: Report from a Brazilian reference center
Abstract Treatment of moderate and severe forms of osteogenesis imperfecta (OI) with cyclic pamidronate at the Reference Center for OI Treatment in Southern Brazil was studied. A retrospective cohort study was conducted from 2002 to 2012. Data were obtained during inpatient (drug infusion) and outpatient care. Clinical data, including the presence of blue sclerae, dentinogenesis imperfecta, history and site of the fractures, biochemical data, including calcium, phosphorus, and alkaline phosphatase levels, were systematically collected. Bone mineral density (BMD) was measured using dual energy X-ray absorptiometry (DXA). Fo...
Source: Genetics and Molecular Biology - July 16, 2019 Category: Genetics & Stem Cells Source Type: research
State biomarkers for Machado Joseph disease: Validation, feasibility and responsiveness to change
We present here a review of studies on peripheral and neurophysiological markers in SCA3/MJD that can be candidates for state biomarkers. Data on markers already studied were summarized, giving emphasis on validation against clinical scale, and responsiveness to change. While some biological fluid compounds and neurophysiological parameters showed poor responsiveness, others seemed to be good candidates. Some potential candidates that are waiting for responsiveness studies were serum levels of neuron specific enolase, vestibulo-ocular reflex and video-oculography. Candidates evaluated by RNA and microRNA expression levels ...
Source: Genetics and Molecular Biology - July 16, 2019 Category: Genetics & Stem Cells Source Type: research
Performance of the Gail and Tyrer-Cuzick breast cancer risk assessment models in women screened in a primary care setting with the FHS-7 questionnaire
In this study, our aim was to compare the Gail and Tyrer-Cuzick models after initial screening for familial history of cancer in primary care using the FHS-7 questionnaire. We compared 846 unrelated women with at least one positive answer to any of the seven FHS-7 questions (positive group) and 892 unrelated women that answered negatively (negative group). Concordance between BC risk estimates was compared by Bland-Altman graphics. Mean BC risk estimates were higher using the Tyrer-Cuzick Model in women from the positive group, while women from the negative group had higher BC risk estimates using the Gail model. With incr...
Source: Genetics and Molecular Biology - July 16, 2019 Category: Genetics & Stem Cells Source Type: research
Reviewing the characteristics of BRCA and PALB2-related cancers in the precision medicine era
Abstract Germline mutations in BRCA1 and BRCA2 (BRCA) genes confer high risk of developing cancer, especially breast and ovarian tumors. Since the cloning of these tumor suppressor genes over two decades ago, a significant amount of research has been done. Most recently, monoallelic loss-of-function mutations in PALB2 have also been shown to increase the risk of breast cancer. The identification of BRCA1, BRCA2 and PALB2 as proteins involved in DNA double-strand break repair by homologous recombination and of the impact of complete loss of BRCA1 or BRCA2 within tumors have allowed the development of novel therapeutic appro...
Source: Genetics and Molecular Biology - July 16, 2019 Category: Genetics & Stem Cells Source Type: research
Phenotype-oriented NGS panels for mucopolysaccharidoses: Validation and potential use in the diagnostic flowchart
Abstract Mucopolysaccharidosis (MPS) are a group of rare genetic disorders caused by deficiency in the activity of specific lysosomal enzymes required for the degradation of glycosaminoglycans (GAGs). A defect in the activity of these enzymes will result in the abnormal accumulation of GAGs inside the lysosomes of most cells, inducing progressive cellular damage and multiple organ failure. DNA samples from 70 patients with biochemical diagnosis of different MPSs genotypes confirmed by Sanger sequencing were used to evaluate a Next Generation Sequencing (NGS) protocol. Eleven genes related to MPSs were divided into three di...
Source: Genetics and Molecular Biology - July 16, 2019 Category: Genetics & Stem Cells Source Type: research
Sensitivity, advantages, limitations, and clinical utility of targeted next-generation sequencing panels for the diagnosis of selected lysosomal storage disorders
We report the assessment of a NGS approach as a new tool in the diagnosis of LSDs in our service. (Source: Genetics and Molecular Biology)
Source: Genetics and Molecular Biology - July 16, 2019 Category: Genetics & Stem Cells Source Type: research
Integrated analysis of the critical region 5p15.3–p15.2 associated with cri-du-chat syndrome
Abstract Cri-du-chat syndrome (CdCs) is one of the most common contiguous gene syndromes, with an incidence of 1:15,000 to 1:50,000 live births. To better understand the etiology of CdCs at the molecular level, we investigated theprotein – protein interaction (PPI) network within the critical chromosomal region 5p15.3 – p15.2 associated with CdCs using systemsbiology. Data were extracted from cytogenomic findings from patients with CdCs. Based on clinical findings, molecular characterization of chromosomal rearrangements, and systems biology data, we explored possible genotype – phenotype correlations involving biolo...
Source: Genetics and Molecular Biology - July 16, 2019 Category: Genetics & Stem Cells Source Type: research
Screening for organic acidurias and aminoacidopathies in high-risk Brazilian patients: Eleven-year experience of a reference center
Abstract Organic acidurias and aminoacidopathies are groups of frequent inborn errors of metabolism (IEMs), which are caused by mutations in specific genes that lead to loss of protein/enzyme or transport function with important deleterious effects to cell metabolism. Since a considerable number of such disorders are potentially treatable when diagnosed at an early stage of life, diagnosis is crucial for the patients. In the present report, we describe symptomatic individuals referred to our service that were diagnosed with these disorders from 2006 to 2016. We used blood and urine samples from 21,800 patients suspected of...
Source: Genetics and Molecular Biology - July 16, 2019 Category: Genetics & Stem Cells Source Type: research
Lysosomal diseases: Overview on current diagnosis and treatment
Abstract Lysosomal diseases (LDs), also known as lysosomal storage diseases (LSDs), are a heterogeneous group of conditions caused by defects in lysosomal function. LDs may result from deficiency of lysosomal hydrolases, membrane-associated transporters or other non-enzymatic proteins. Interest in the LD field is growing each year, as more conditions are, or will soon be treatable. In this article, we review the diagnosis of LDs, from clinical suspicion and screening tests to the identification of enzyme or protein deficiencies and molecular genetic diagnosis. We also cover the treatment approaches that are currently avail...
Source: Genetics and Molecular Biology - July 16, 2019 Category: Genetics & Stem Cells Source Type: research
Information and Diagnosis Networks – tools to improve diagnosis and treatment for patients with rare genetic diseases
Abstract Brazil is a country of continental dimensions and most genetic services are concentrated in the Southeast and South, including the Medical Genetics Service of the Hospital de Cl ínicas de Porto Alegre (MGS/HCPA). As many areas on the country do not have adequate medical genetics support, networks were designed to extend the service of the MGS/HCPA reference center. This paper presents the information and diagnosis networks that have their headquarters at MGS/HCPA: SIAT (Na tional Information System on Teratogenic Agents), SIEM (Information Service on Inborn Errors of Metabolism), Alô Genética (Hello Genetics - ...
Source: Genetics and Molecular Biology - July 16, 2019 Category: Genetics & Stem Cells Source Type: research
Medical Genetics – Special issue dedicated to the 35th anniversary of the Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Brazil
(Source: Genetics and Molecular Biology)
Source: Genetics and Molecular Biology - July 16, 2019 Category: Genetics & Stem Cells Source Type: research
Erratum
Abstract The filter cake from sugar cane processing is rich in organic matter and nutrients, which favors the proliferation of microorganisms with potential to deconstruct plant biomass. From the metagenomic data of this material, we assembled a draft genome that was phylogenetically related to Thermomonospora curvata DSM 43183, which shows the functional and ecological importance of this bacterium in the filter cake. Thermomonospora is a gram-positive bacterium that produces cellulases in compost, and it can survive temperatures of 60 ºC. We identified a complete set of biomass depolymerizing enzymes in the draft genome ...
Source: Genetics and Molecular Biology - March 19, 2019 Category: Genetics & Stem Cells Source Type: research
