Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 574
Filtrar
1.
Nat Genet ; 51(4): 579, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30926967
2.
Genome Med ; 11(1): 9, 2019 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-30795816

RESUMO

Genomic medicine has considerable potential to provide novel diagnostic and therapeutic solutions for patients who have molecularly complex diseases and who are not responding to existing therapies. To bridge the gap between genomic medicine and clinical practice, integration of various data types, resources, and joint international initiatives will be required.


Assuntos
Terapia Genética/métodos , Genética Médica/métodos , Genômica/métodos , Pesquisa Médica Translacional/métodos , Humanos
3.
Eur J Hum Genet ; 27(3): 484-487, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30568241

RESUMO

Clinical trials using somatic gene editing (e.g., CRISPR-Cas9) have started in Europe and the United States and may provide safe and effective treatment and cure, not only for cancers but also for some monogenic conditions. In a workshop at the 2018 European Human Genetics Conference, the challenges of bringing somatic gene editing therapies to the clinic were discussed. The regulatory process needs to be considered early in the clinical development pathway to produce the data necessary to support the approval by the European Medicines Agency. The roles and responsibilities for geneticists may include counselling to explain the treatment possibilities and safety interpretation.


Assuntos
Congressos como Assunto , Terapia Genética/métodos , Genética Médica/métodos , Sistemas CRISPR-Cas , Ensaios Clínicos como Assunto , Edição de Genes/métodos , Humanos
4.
Pediatr Rev ; 39(7): 323-331, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29967077

RESUMO

Genetic counseling is a communication process whereby an individual or family obtains information about a genetic condition, is helped to understand the implications and significance of the condition, and is given resources to help with coping and management. It is a continuous process involving lasting supportive relationships between the family and the genetic professional. Genetic counselors are master's level-trained health-care professionals who work closely with pediatricians and pediatric subspecialists alike. Genetic counselors can be a source of information about genetic conditions, risk assessment for disease, and genetic testing. Although most of a genetic counselor's job is patient care and education, genetic counselors also serve as resources to educate health professionals about genetics.


Assuntos
Aconselhamento Genético , Pediatria , Criança , Conselheiros , Testes Genéticos/métodos , Genética Médica/métodos , Humanos
5.
Rev. cuba. salud pública ; 44(2): 360-373, abr.-jun. 2018. tab
Artigo em Espanhol | LILACS | ID: biblio-901570

RESUMO

Introducción: Las nuevas tecnologías disponibles en el campo de la genética humana y médica pueden ser utilizadas, cada vez más, con fines médicos preventivos. Existe también el riesgo de su uso indebido que favorezca la discriminación y la eutanasia selectiva y minimice el papel de los condicionantes sociales en la salud de las poblaciones. Objetivo: Establecer normas éticas para garantizar que las pruebas presintomáticas en Cuba se realicen conforme a los principios éticos de respeto a la autonomía, justicia, beneficencia y no maleficencia. Métodos: Estas normas se elaboraron a partir de una propuesta discutida y consensuada en talleres nacionales con la participación de genetistas clínicos de todo el país y aprobadas por el Comité de Ética del Centro Nacional de Genética Médica y el Ministerio de Salud Pública. Resultados: Las normas aprobadas consideraron aspectos esenciales como el conocimiento sobre el alcance de la información que la prueba revelará y sus implicaciones a nivel personal y familiar, el consentimiento informado para su realización, las condiciones en que se realiza y la seguridad de sus resultados, las obligaciones médicas antes, durante y después de la realización de la prueba y lo concerniente a la privacidad y confidencialidad de la información. Conclusiones: La generalización y cumplimiento de las normas aprobadas asegura la protección a individuos y familias vulnerables, contribuye a mejorar su atención médica y a aminorar el impacto que sobre su salud, su reproducción y su vida en general, tienen las severas enfermedades para las que están en riesgo o padecen(AU)


Introduction: New technologies available in the field of human and medical genetics can increasingly be used for preventive medical purposes. There is also the risk of misuse that favors discrimination and selective euthanasia, and that minimizes the role of social determinants in the health of the populations. Objectives: To establish ethical norms to ensure that presymptomatic tests in Cuba are carried out in accordance with the principles of respect for autonomy, justice, beneficence and non-malice. Methods: These norms were elaborated from a proposal discussed and agreed upon in national workshops with the participation of clinical geneticists from all over the country and approved by the Ethics Committee of the National Center of Medical Genetics and the Ministry of Public Health. Results: The approved norms considered essential aspects such as: the knowledge about the scope of information that the test will reveal and its implications on a personal and family level, informed consent for its implementation, the conditions under which it is performed, and the safety of its results; medical obligations before, during and after the performance of the test; and all concerning to the privacy and confidentiality of the information. Conclusions: The generalization and compliance of these ethical norms ensure the protection of vulnerable individuals and families, contributes to improving their medical care and to reducing the impact on their health, their reproduction and life in general terms of the severe diseases they are at risk or suffering from(AU)


Assuntos
Humanos , Ética Médica/educação , Genética Médica/métodos , Cuba , Aconselhamento Genético/métodos , Genética Médica/normas
6.
Gac. sanit. (Barc., Ed. impr.) ; 32(1): 92-95, ene.-feb. 2018. tab
Artigo em Espanhol | IBECS | ID: ibc-170159

RESUMO

Los diseños genéticamente informativos, y en particular los estudios de gemelos, constituyen la metodología más utilizada para analizar la contribución relativa de los factores genéticos y ambientales a la variabilidad interindividual. Básicamente, consisten en comparar el grado de similitud, con respecto a una característica o rasgo determinado, entre gemelos monocigóticos y dicigóticos. Además de la clásica estimación de heredabilidad, este tipo de registros permite una amplia variedad de análisis únicos por las características de la muestra. El Registro de Gemelos de Murcia es un registro de base poblacional centrado en el análisis de conductas relacionadas con la salud. Las prevalencias de problemas de salud observadas son comparables a las de otras muestras de referencia de ámbito regional y estatal, lo que avala su representatividad. En conjunto, sus características facilitan el desarrollo de diversas modalidades de investigación, además de diseños genéticamente informativos y la colaboración con distintas iniciativas y consorcios (AU)


Genetically informative designs and, in particular, twin studies, are the most widely used methodology to analyse the relative contribution of genetic and environmental factors to inter-individual variability. These studies basically compare the degree of phenotypical similarity between monozygotic and dizygotic twin pairs. In addition to the traditional estimate of heritability, this kind of registry enables a wide variety of analyses which are unique due to the characteristics of the sample. The Murcia Twin Registry is population-based and focused on the analysis of health-related behaviour. The observed prevalence of health problems is comparable to that of other regional and national reference samples, which guarantees its representativeness. Overall, the characteristics of the Registry facilitate developing various types of research as well as genetically informative designs, and collaboration with different initiatives and consortia (AU)


Assuntos
Humanos , Gêmeos/genética , Estudos em Gêmeos como Assunto/métodos , Registros/normas , Sistema de Registros/ética , Sistema de Registros/normas , Estudos em Gêmeos como Assunto/ética , Genética Médica/métodos , Genética Comportamental/ética , Genética Comportamental/métodos
7.
Genet Med ; 20(2): 169-171, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29323668

RESUMO

Disclaimer: This Points to Consider document is designed as an educational resource to provide best practices for medical genetic clinicians, laboratories, and journals regarding the provision, publication, and dissemination of patient phenotypes in the context of genomic testing, clinical genetic practice, and research. While the goal of the document is the improvement of patient care, the considerations and practices described should not be considered inclusive of all proper considerations and practices or exclusive of others that are reasonably directed to obtaining the same goal. In determining the value of any practice, clinicians, laboratories, and journals should apply their own professional standards and judgment to the specific circumstances presented.The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the authors' affiliated institutions.


Assuntos
Testes Genéticos/normas , Genética Médica/normas , Genômica/normas , Disseminação de Informação , Papel Profissional , Publicações/normas , Testes Genéticos/métodos , Genética Médica/métodos , Genômica/métodos , Humanos
8.
Genet Med ; 20(1): 83-90, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28661487

RESUMO

PurposeTesting for inborn errors of metabolism is performed by clinical laboratories worldwide, each utilizing laboratory-developed procedures. We sought to summarize performance in the College of American Pathologists' (CAP) proficiency testing (PT) program and identify opportunities for improving laboratory quality. When evaluating PT data, we focused on a subset of laboratories that have participated in at least one survey since 2010.MethodsAn analysis of laboratory performance (2004 to 2014) on the Biochemical Genetics PT Surveys, a program administered by CAP and the American College of Medical Genetics and Genomics. Analytical and interpretive performance was evaluated for four tests: amino acids, organic acids, acylcarnitines, and mucopolysaccharides.ResultsSince 2010, 150 laboratories have participated in at least one of four PT surveys. Analytic sensitivities ranged from 88.2 to 93.4%, while clinical sensitivities ranged from 82.4 to 91.0%. Performance was higher for US participants and for more recent challenges. Performance was lower for challenges with subtle findings or complex analytical patterns.ConclusionUS clinical biochemical genetics laboratory proficiency is satisfactory, with a minority of laboratories accounting for the majority of errors. Our findings underscore the complex nature of clinical biochemical genetics testing and highlight the necessity of continuous quality management.


Assuntos
Testes Genéticos/normas , Laboratórios/normas , Ensaio de Proficiência Laboratorial/métodos , Ensaio de Proficiência Laboratorial/normas , Testes Genéticos/métodos , Genética Médica/métodos , Genética Médica/normas , Humanos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
9.
Genet Med ; 20(1): 31-41, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28726809

RESUMO

PurposeWe integrated whole-exome sequencing (WES) and chromosomal microarray analysis (CMA) into a clinical workflow to serve an endogamous, uninsured, agrarian community.MethodsSeventy-nine probands (newborn to 49.8 years) who presented between 1998 and 2015 remained undiagnosed after biochemical and molecular investigations. We generated WES data for probands and family members and vetted variants through rephenotyping, segregation analyses, and population studies.ResultsThe most common presentation was neurological disease (64%). Seven (9%) probands were diagnosed by CMA. Family WES data were informative for 37 (51%) of the 72 remaining individuals, yielding a specific genetic diagnosis (n = 32) or revealing a novel molecular etiology (n = 5). For five (7%) additional subjects, negative WES decreased the likelihood of genetic disease. Compared to trio analysis, "family" WES (average seven exomes per proband) reduced filtered candidate variants from 22 ± 6 to 5 ± 3 per proband. Nineteen (51%) alleles were de novo and 17 (46%) inherited; the latter added to a population-based diagnostic panel. We found actionable secondary variants in 21 (4.2%) of 502 subjects, all of whom opted to be informed.ConclusionCMA and family-based WES streamline and economize diagnosis of rare genetic disorders, accelerate novel gene discovery, and create new opportunities for community-based screening and prevention in underserved populations.


Assuntos
Testes Genéticos/estatística & dados numéricos , Genética Médica/métodos , Genética Médica/estatística & dados numéricos , Genômica/estatística & dados numéricos , Disparidades em Assistência à Saúde/estatística & dados numéricos , Populações Vulneráveis , Adolescente , Adulto , Algoritmos , Criança , Pré-Escolar , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Testes Genéticos/métodos , Genômica/métodos , Humanos , Achados Incidentais , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Linhagem , Vigilância da População , Fluxo de Trabalho , Adulto Jovem
10.
Genet Med ; 20(3): 369-373, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29240077

RESUMO

PurposeTo describe the frequency and nature of differences in variant classifications between clinicians and genetic testing laboratories.MethodsRetrospective review of variants identified through genetic testing ordered in routine clinical care by clinicians in the Stanford Center for Inherited Cardiovascular Disease. We compared classifications made by clinicians, the testing laboratory, and other laboratories in ClinVar.ResultsOf 688 laboratory classifications, 124 (18%) differed from the clinicians' classifications. Most differences in classification would probably affect clinical care of the patient and/or family (83%, 103/124). The frequency of discordant classifications differed depending on the testing laboratory (P < 0.0001) and the testing laboratory's classification (P < 0.00001). For the majority (82/124, 66%) of discordant classifications, clinicians were more conservative (less likely to classify a variant pathogenic or likely pathogenic). The clinicians' classification was discordant with one or more submitter in ClinVar in 49.1% (28/57) of cases, while the testing laboratory's classification was discordant with a ClinVar submitter in 82.5% of cases (47/57, P = 0.0002).ConclusionThe clinical team disagreed with the laboratory's classification at a rate similar to that of reported disagreements between laboratories. Most of this discordance was clinically significant, with clinicians tending to be more conservative than laboratories in their classifications.


Assuntos
Variação Genética , Genética Médica/normas , Laboratórios , Anotação de Sequência Molecular/normas , Médicos , Alelos , Estudos de Associação Genética/métodos , Estudos de Associação Genética/normas , Predisposição Genética para Doença , Testes Genéticos/métodos , Testes Genéticos/normas , Genética Médica/métodos , Humanos
11.
Salvador; s.n; 2018. 59 p. ilus.
Tese em Português | LILACS | ID: biblio-1005550

RESUMO

INTRODUÇÃO: As miopatias são doenças cuja etiologia decorre de alterações estruturais e/ou funcionais no músculo esquelético. As miopatias distais são doenças musculares primárias em que fraqueza e, frequentemente atrofia, tem início nas mãos, antebraços, pés e segmento distal das pernas. Apesar de terem sido divididas como um grupo restrito de doenças, outras miopatias podem se manifestar com um padrão distal, como a miopatia nemalínica e as distrofias musculares cintura-membros. Devido à escassez de trabalhos que descrevem clinicamente as miopatias distais, este trabalho visou contribuir com essa caracterização. METODOLOGIA: Os pacientes foram selecionados no ambulatório de doenças neuromusculares do Hospital Universitário Professor Edgar Santos, em seguida avaliados clinicamente, através de exame físico e também com exames complementares: eletroneuromiografia, exames laboratoriais, estudo molecular e histopatológico. RESULTADOS: Quinze pacientes com padrão distal foram analisados, sendo 40% do sexo feminino, média de idade de 29,8 anos, seis (40|%) pacientes naturais da capital, Salvador-Bahia. Quanto ao padrão de distribuição de fraqueza, sete apresentavam padrão distal, enquanto oito, padrão distal-proximal. Os pacientes foram agrupados de acordo com a idade de início dos sintomas, sendo 11 iniciados na infância e adolescência (T em homozigose), um com sarcoglicanopatia (mutação c.229C>T em homozigose) e um com miopatia nemalínica (histopatológico com presença de corpos nemalínicos). DISCUSSÃO: Os achados identificados nos pacientes com diagnósticos firmados foram compatíveis com o que é visto na literatura, como apresentação clínica e mutações identificadas previamente. Destaca-se o componente distal pronunciado da paciente com sarcoglicanopatia, considerado incomum. Além disso, a descrição da ressonância magnética realizada nos indivíduos demonstrou um padrão típico. Na maior parte dos pacientes não se chegou a um diagnóstico etiológico, a despeito da investigação realizada com os exames complementares e clínicos. CONCLUSÃO: O presente estudo caracterizou uma amostra de pacientes com miopatias distais, corroborando que essas doenças se manifestam clinicamente de forma heterogênea. A caracterização e divisão entre grupos visa tornar mais fácil a investigação, devendo ser feita com exames complementares, considerados imprescindíveis para se estabelecer o diagnóstico etiológico dessas doenças


INTRODUCTION: Myopathies are diseases which etiology results from structural and/or functional changes in skeletal muscle. Distal myopathies are a group of muscular pathologies in which weakness and atrophy begins and predominates in distal limbs, like hands and feet. Although it has been divided as a restrict group of diseases, other myopathies can manifest with that pattern of weakness, such nemaline myopathy and limb-girdle muscular dystrophies. Due to the scarcity of studies that described clinically the distal myopathies, this study focuses on clinical characterization of myopathies with distal pattern of weakness. METHODOLOGY: The patients were selected in the outpatient clinic for neuromuscular diseases at Professor Edgar Santos University Hospital. Those subjects were clinically evaluated through physical examination, laboratory tests, electroneuromyography, magnetic resonance (MRI) and histopathological study. RESULTS: Fifteen patients with distal pattern were analyzed, being 40% female, mean age 29.8 years, six (40 %) patients were born in the capital, Salvador-Bahia. As for the pattern of weakness distribution, seven had an exclusive distal pattern, while eight had a distal-proximal pattern. Patients were grouped according to the age of onset of symptoms, of which 11 were initiated in childhood and adolescence ( T in homozygous in exon 53 in another and one patient were diagnosed by biopsy), one with sarcoglicanopathy (mutation c.229C> T in homozygous) and one with nemaline myopathy (histopathological with the presence of nemalinic bodies). DISCUSSION: The findings identified in patients with established diagnoses were compatible with what is seen in the literature, such as clinical presentation and previously identified mutations. We highlight the pronounced distal component of the patient with sarcoglicanopathy, considered to be uncommon. In addition, the description of MRI performed in the individuals demonstrated a typical pattern. Most of the patients were not diagnosed, despite the research done with the complementary and clinical exams. CONCLUSION: The present study characterized a sample of patients with distal myopathies, corroborating that these diseases manifest themselves clinically heterogeneously. The characterization and division between groups aims to make the investigation easier, and should be done with complementary tests, considered essential to establish the etiological diagnosis of these diseases


Assuntos
Humanos , Genética Médica/métodos , Genética Médica/estatística & dados numéricos , Doenças Musculares/diagnóstico , Doenças Musculares/imunologia , Doenças Musculares/patologia , Doenças Musculares/prevenção & controle
12.
Perspect Biol Med ; 61(4): 503-516, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30613033

RESUMO

Genomics has revealed that biological causation is subtler than a pointillist dream of essentially enumerable, additive precision predictability from constitutive DNA sequences. Instead, data have revealed a higher-dimension interactive genomic landscape, that is more fundamentally fluid than precision predictability requires. This raises epistemological and ontological issues that, if properly accepted, may help leverage new ideas.


Assuntos
Genética Médica/métodos , Genômica/métodos , Biologia Computacional , Expressão Gênica , Estudo de Associação Genômica Ampla , Haplótipos , Humanos , Conhecimento , Estilo de Vida , Probabilidade
13.
Genome Med ; 9(1): 112, 2017 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-29254491

RESUMO

Peter M. Visscher discusses advances in our understanding of complex disease, the challenges in applying this knowledge to functional follow-up, and the potential implications for therapeutic interventions.


Assuntos
Predisposição Genética para Doença , Herança Multifatorial , Genética Médica/métodos , Genoma Humano , Estudo de Associação Genômica Ampla/métodos , Humanos
15.
Nat Genet ; 49(10): 1495-1501, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28892063

RESUMO

Identifying regions of the genome that are depleted of mutations can distinguish potentially deleterious variants. Short tandem repeats (STRs), also known as microsatellites, are among the largest contributors of de novo mutations in humans. However, per-locus studies of STR mutations have been limited to highly ascertained panels of several dozen loci. Here we harnessed bioinformatics tools and a novel analytical framework to estimate mutation parameters for each STR in the human genome by correlating STR genotypes with local sequence heterozygosity. We applied our method to obtain robust estimates of the impact of local sequence features on mutation parameters and used these estimates to create a framework for measuring constraint at STRs by comparing observed versus expected mutation rates. Constraint scores identified known pathogenic variants with early-onset effects. Our metric will provide a valuable tool for prioritizing pathogenic STRs in medical genetics studies.


Assuntos
Aptidão Genética , Genética Médica/métodos , Instabilidade de Microssatélites , Repetições de Microssatélites , Taxa de Mutação , Biologia Computacional/métodos , Diploide , Evolução Molecular , Doenças Genéticas Inatas/genética , Genótipo , Heterozigoto , Humanos , Modelos Genéticos , Anotação de Sequência Molecular
17.
Genet Med ; 19(10)2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28682309

RESUMO

Disclaimer: These ACMG Standards and Guidelines are intended as an educational resource for clinical laboratory geneticists to help them provide quality clinical laboratory genetic services. Adherence to these Standards and Guidelines is voluntary and does not necessarily assure a successful medical outcome. These Standards and Guidelines should not be considered inclusive of all proper procedures and tests or exclusive of others that are reasonably directed to obtaining the same results. In determining the propriety of any specific procedure or test, clinical laboratory geneticists should apply their professional judgment to the specific circumstances presented by the patient or specimen. Clinical laboratory scientists and geneticists are encouraged to document in the patient's record the rationale for the use of a particular procedure or test, whether or not it is in conformance with these Standards and Guidelines. They also are advised to take notice of the date any particular guideline was adopted, and to consider other relevant medical and scientific information that becomes available after that date. It also would be prudent to consider whether intellectual property interests may restrict the performance of certain tests and other procedures.Biotinidase deficiency is an autosomal recessively inherited disorder of biotin recycling that is associated with neurologic and cutaneous consequences if untreated. Fortunately, the clinical features of the disorder can be ameliorated or prevented by administering pharmacological doses of the vitamin biotin. Newborn screening and confirmatory diagnosis of biotinidase deficiency encompasses both enzymatic and molecular testing approaches. These guidelines were developed to define and standardize laboratory procedures for enzymatic biotinidase testing, to delineate situations for which follow-up molecular testing is warranted, and to characterize variables that can influence test performance and interpretation of results.


Assuntos
Deficiência de Biotinidase/diagnóstico , Testes Genéticos/normas , Biotinidase/metabolismo , Técnicas de Laboratório Clínico , Feminino , Genética Médica/métodos , Genômica/normas , Humanos , Recém-Nascido , Masculino , Triagem Neonatal , Estados Unidos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA