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1.
Exp Suppl ; 111: 29-32, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31588526

RESUMO

In this brief chapter, clinically very important topics of family screening and genetic counseling are discussed that are also pivotal in endocrine genetics. Genetic screening makes possible to diagnose a genetic disease at an early stage or to exclude its presence. Family members have to be screened if a heritable disease is diagnosed. Personal consultation with the patient and the relatives is inevitable in every genetically determined disease. The main function of genetic counseling is the transfer of important pieces of information to the patient about the congenital or later-manifesting diseases. This process via the informed consent should give enough information to the patient and the relatives to make decisions about the disease. Genetic data should be considered as special data; therefore the protection of the personal data and the confidentiality obligation should be prevailed intensively. The chief goal of the genetic counseling is the prevention of the conception or the birth of a person who would suffer from a severe genetic disease and/or to present information of the chance for having an affected descendant. If the prevention is not feasible, the alternative aim is to prevent the development of the consequences or to moderate its severity. Genetic counseling has important ethical aspects such as prenatal genetic investigations; hereditary, but treatable, nonlethal diseases; and genetic diseases that manifest late, predominantly in the adulthood.


Assuntos
Saúde da Família , Aconselhamento Genético , Testes Genéticos , Confidencialidade , Humanos , Consentimento Livre e Esclarecido
2.
Exp Suppl ; 111: 245-260, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31588535

RESUMO

Congenital adrenal hyperplasia (CAH) is a group of seven autosomal recessively inherited disorders of various enzymes participating in adrenal steroid hormone synthesis. Patients present with various symptoms depending on the nature and severity of the enzymatic block. More than 95% of all CAH patients suffer from 21-hydroxylase deficiency. The genetic background is well characterized for all CAH subtypes. Characterization of their genetic background has provided important pathophysiologic understanding of steroid biosynthesis disorders. Genotyping is important for confirming diagnosis, determining prognostic factors, and for genetic counseling for family planning and may reveal new therapeutic approaches.


Assuntos
Hiperplasia Suprarrenal Congênita/genética , Patrimônio Genético , Hiperplasia Suprarrenal Congênita/diagnóstico , Aconselhamento Genético , Humanos
3.
Med Clin North Am ; 103(6): 1077-1092, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31582005

RESUMO

Compared to clinicians previously surveyed, primary care providers employed in a health system known for clinical genomics were more likely to have ordered or referred a patient for genetic testing, but had only modestly more genetics training and reported similarly low levels of comfort answering patient questions about genetic risk. Most supported population genomic screening, reported willingness to get screened themselves, and judged a hypothetical patient's decision to be screened favorably relative to a similar patient's decision to decline screening. Stakeholder perceptions of the ethical appropriateness of nudging at-risk patients to discuss testing with counselors were mixed.


Assuntos
Aconselhamento Genético , Testes Genéticos/métodos , Atenção Primária à Saúde , Aconselhamento Genético/ética , Aconselhamento Genético/métodos , Aconselhamento Genético/psicologia , Humanos , Medicina de Precisão/métodos , Atenção Primária à Saúde/métodos , Atenção Primária à Saúde/tendências , Sequenciamento Completo do Exoma
4.
Med Clin North Am ; 103(6): 967-976, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31582007

RESUMO

Historically, both pretest and posttest genetic counseling has been standard of care for genetic testing. This model should be adapted for primary care providers (PCPs) willing to learn critical information about the test and key concepts that patients need to make an informed testing decision. It is helpful for PCPs to discuss a few initial patients with a genetic counselor to prepare for the key concepts of pretest and posttest counseling. This article provides guidance about the recommended level of involvement of PCPs based on the test indication, test complexity, disorder management, and the potential for psychosocial sequela.


Assuntos
Revelação , Aconselhamento Genético , Atenção Primária à Saúde , Aconselhamento Genético/ética , Aconselhamento Genético/métodos , Aconselhamento Genético/psicologia , Humanos , Guias de Prática Clínica como Assunto , Atenção Primária à Saúde/métodos , Atenção Primária à Saúde/normas
6.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(8): 765-768, 2019 Aug 10.
Artigo em Chinês | MEDLINE | ID: mdl-31400123

RESUMO

OBJECTIVE: To detect potential mutations of the PKHD1 gene in two pedigrees affected with infantile polycystic kidney disease. METHODS: Clinical data and peripheral venous blood samples were collected from the probands and their parents as well as fetal amniotic fluid cells. Genome DNA was extracted from the peripheral blood samples and amniotic fluid cells. Exons 32 and 61 of the PKHD1 gene were amplified with PCR and subjected to direct sequencing. RESULTS: The proband of pedigree 1 was found to carry c.4274T>G (p.Leu1425Arg) mutation in exon 32 and c.10445G>C (p.Arg3482Pro) mutation in exon 61 of the PKHD1 gene, which were inherited from her father and mother, respectively. The fetus has carried the c.4274T>G (p.Leu1425Arg) mutation. In pedigree 2, the wife and her husband had respectively carried a heterozygous c.5979_5981delTGG mutation and a c.9455delA mutation of the PKHD1 gene. No chromosomal aberration was found in the umbilical blood sample, but the genetic testing of their fetus was failed. Based on software prediction, all of the 4 mutations were predicted to be pathogenic. CONCLUSION: PKHD1 c.4274T>G (p.Leu1425Arg), c.10445G>C (p.Arg3482Pro), c.5979_5981delTGG and c.9455delA were likely to be pathogenic mutations. The results have facilitated genetic counseling and prenatal diagnosis for the two pedigrees.


Assuntos
Aconselhamento Genético , Doenças Renais Policísticas/diagnóstico , Doenças Renais Policísticas/genética , Diagnóstico Pré-Natal , Receptores de Superfície Celular/efeitos dos fármacos , Análise Mutacional de DNA , Feminino , Humanos , Mutação , Linhagem , Gravidez
8.
Yi Chuan ; 41(8): 746-753, 2019 Aug 20.
Artigo em Chinês | MEDLINE | ID: mdl-31447425

RESUMO

Personal genomic information benefits from accumulated big data and its application is no longer limited to scientific research. Presently, it is undergoing the transformation to daily medical practice. Systematic arrangement, archiving and rational utilization of disease-related genomic information is an important foundation of future precision medicine. Hemoglobinopathy is prevalent in southern China, but its molecular pathological basis has racial specificity. To facilitate clinical diagnosis and genetic screening of hemoglobinopathy in southern China, we established the LOVD gene data management system for the variation and phenotype spectrum of hemoglobinopathy. Then we designed an integrated and efficient on-line auxiliary accurate diagnosis and risk assessment system in order to assist clinicians to make comprehensive diagnosis and genetic counseling in a short time based on cloud standardized annotated library of specific hemoglobinopathy variants and diagnostic repository. The methodology and experience of improving the clinical decision-making efficiency of diseases with big data and artificial intelligence technology can be used as an example in the clinical and preventive application of other diseases.


Assuntos
Bases de Dados Genéticas , Sistemas de Apoio a Decisões Clínicas , Hemoglobinopatias/genética , Mutação , China , Aconselhamento Genético , Testes Genéticos , Humanos
10.
JAMA ; 322(7): 666-685, 2019 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-31429902

RESUMO

Importance: Pathogenic mutations in breast cancer susceptibility genes BRCA1 and BRCA2 increase risks for breast, ovarian, fallopian tube, and peritoneal cancer in women; interventions reduce risk in mutation carriers. Objective: To update the 2013 US Preventive Services Task Force review on benefits and harms of risk assessment, genetic counseling, and genetic testing for BRCA1/2-related cancer in women. Data Sources: Cochrane libraries; MEDLINE, PsycINFO, EMBASE (January 1, 2013, to March 6, 2019, for updates; January 1, 1994, to March 6, 2019, for new key questions and populations); reference lists. Study Selection: Discriminatory accuracy studies, randomized clinical trials (RCTs), and observational studies of women without recently diagnosed BRCA1/2-related cancer. Data Extraction and Synthesis: Data on study methods, setting, population characteristics, eligibility criteria, interventions, numbers enrolled and lost to follow-up, outcome ascertainment, and results were abstracted. Two reviewers independently assessed study quality. Main Outcomes and Measures: Cancer incidence and mortality; discriminatory accuracy of risk assessment tools for BRCA1/2 mutations; benefits and harms of risk assessment, genetic counseling, genetic testing, and risk-reducing interventions. Results: For this review, 103 studies (110 articles; N = 92 712) were included. No studies evaluated the effectiveness of risk assessment, genetic counseling, and genetic testing in reducing incidence and mortality of BRCA1/2-related cancer. Fourteen studies (n = 43 813) of 8 risk assessment tools to guide referrals to genetic counseling demonstrated moderate to high accuracy (area under the receiver operating characteristic curve, 0.68-0.96). Twenty-eight studies (n = 8060) indicated that genetic counseling was associated with reduced breast cancer worry, anxiety, and depression; increased understanding of risk; and decreased intention for testing. Twenty studies (n = 4322) showed that breast cancer worry and anxiety were higher after testing for women with positive results and lower for others; understanding of risk was higher after testing. In 8 RCTs (n = 54 651), tamoxifen (relative risk [RR], 0.69 [95% CI, 0.59-0.84]; 4 trials), raloxifene (RR, 0.44 [95% CI, 0.24-0.80]; 2 trials), and aromatase inhibitors (RR, 0.45 [95% CI, 0.26-0.70]; 2 trials) were associated with lower risks of invasive breast cancer compared with placebo; results were not specific to mutation carriers. Mastectomy was associated with 90% to 100% reduction in breast cancer incidence (6 studies; n = 2546) and 81% to 100% reduction in breast cancer mortality (1 study; n = 639); oophorectomy was associated with 69% to 100% reduction in ovarian cancer (2 studies; n = 2108); complications were common with mastectomy. Conclusions and Relevance: Among women without recently diagnosed BRCA1/2-related cancer, the benefits and harms of risk assessment, genetic counseling, and genetic testing to reduce cancer incidence and mortality have not been directly evaluated by current research.


Assuntos
Neoplasias da Mama/genética , Genes BRCA1 , Genes BRCA2 , Aconselhamento Genético , Testes Genéticos , Mutação , Neoplasias Ovarianas/genética , Neoplasias da Mama/prevenção & controle , Neoplasias das Tubas Uterinas/genética , Neoplasias das Tubas Uterinas/prevenção & controle , Feminino , Predisposição Genética para Doença , Humanos , Neoplasias Ovarianas/prevenção & controle , Neoplasias Peritoneais/genética , Neoplasias Peritoneais/prevenção & controle , Medição de Risco
11.
JAMA ; 322(7): 652-665, 2019 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-31429903

RESUMO

Importance: Potentially harmful mutations of the breast cancer susceptibility 1 and 2 genes (BRCA1/2) are associated with increased risk for breast, ovarian, fallopian tube, and peritoneal cancer. For women in the United States, breast cancer is the most common cancer after nonmelanoma skin cancer and the second leading cause of cancer death. In the general population, BRCA1/2 mutations occur in an estimated 1 in 300 to 500 women and account for 5% to 10% of breast cancer cases and 15% of ovarian cancer cases. Objective: To update the 2013 US Preventive Services Task Force (USPSTF) recommendation on risk assessment, genetic counseling, and genetic testing for BRCA-related cancer. Evidence Review: The USPSTF reviewed the evidence on risk assessment, genetic counseling, and genetic testing for potentially harmful BRCA1/2 mutations in asymptomatic women who have never been diagnosed with BRCA-related cancer, as well as those with a previous diagnosis of breast, ovarian, tubal, or peritoneal cancer who have completed treatment and are considered cancer free. In addition, the USPSTF reviewed interventions to reduce the risk for breast, ovarian, tubal, or peritoneal cancer in women with potentially harmful BRCA1/2 mutations, including intensive cancer screening, medications, and risk-reducing surgery. Findings: For women whose family or personal history is associated with an increased risk for harmful mutations in the BRCA1/2 genes, or who have an ancestry associated with BRCA1/2 gene mutations, there is adequate evidence that the benefits of risk assessment, genetic counseling, genetic testing, and interventions are moderate. For women whose personal or family history or ancestry is not associated with an increased risk for harmful mutations in the BRCA1/2 genes, there is adequate evidence that the benefits of risk assessment, genetic counseling, genetic testing, and interventions are small to none. Regardless of family or personal history, the USPSTF found adequate evidence that the overall harms of risk assessment, genetic counseling, genetic testing, and interventions are small to moderate. Conclusions and Recommendation: The USPSTF recommends that primary care clinicians assess women with a personal or family history of breast, ovarian, tubal, or peritoneal cancer or who have an ancestry associated with BRCA1/2 gene mutations with an appropriate brief familial risk assessment tool. Women with a positive result on the risk assessment tool should receive genetic counseling and, if indicated after counseling, genetic testing. (B recommendation) The USPSTF recommends against routine risk assessment, genetic counseling, or genetic testing for women whose personal or family history or ancestry is not associated with potentially harmful BRCA1/2 gene mutations. (D recommendation).


Assuntos
Neoplasias da Mama/genética , Genes BRCA1 , Genes BRCA2 , Aconselhamento Genético , Testes Genéticos , Mutação , Neoplasias Ovarianas/genética , Neoplasias da Mama/prevenção & controle , Neoplasias das Tubas Uterinas/genética , Feminino , Predisposição Genética para Doença , Humanos , Neoplasias Ovarianas/prevenção & controle , Neoplasias Peritoneais/genética , Medição de Risco
13.
Gene ; 719: 144007, 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31357024

RESUMO

Congenital bilateral absence of vas deferens (CBAVD), a frequent cause of obstructive azoospermia and male infertility in Chinese, is mainly due to mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. This study aim to explore the promoter region of CFTR gene in CBAVD patients and study the mutations by functional analysis, and to discuss the significance of mutation testing in this area. We performed screening analysis on 65 CBAVD patients and 50 controls to detect mutations in the CFTR gene, and studied the functions of promoter mutations using reporter gene constructs, transient transfection techniques and subsequent assessment of transcriptional activity and expression levels. Mutations c.-195C>A and c.-34C>T in the promoter region of the CFTR gene were detected in 4 of our Chinese CBAVD patients, one of which was novel (c.-195C>A) and located in the conservative area, as well as the binding site of SP1 transcription factor through the prediction of bioinformatics analysis. By reverse transcription qPCR assay and luciferase assay, we validated it as a functional disease-causing variant that down-regulates the CFTR gene expression, and this effect was related to the amount of transcription factors. This study was the first to explore the promoter region of the CFTR gene in Chinese, and we believe that mutations in this region are associated with Chinese CBAVD patients. We also suggest a systematic strategy for genotyping Chinese CBAVD couples, which should help in developing reproductive counseling.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Doenças Urogenitais Masculinas/genética , Mutação , Regiões Promotoras Genéticas , Ducto Deferente/anormalidades , Adulto , Linhagem Celular , China , Regulação para Baixo , Genes Reguladores , Aconselhamento Genético , Humanos , Masculino , Reprodução , Adulto Jovem
14.
Gan To Kagaku Ryoho ; 46(7): 1109-1113, 2019 Jul.
Artigo em Japonês | MEDLINE | ID: mdl-31296812

RESUMO

Recently, olaparib(brand name: Lynparza Tablets)-a PARP inhibitor-has been approved for national health insurance coverage in Japan as a drug for unresectable or recurrent, BRCA1/2-positive, HER2-negative breast cancer in patients with a history of cancer chemotherapy. The addition of BRCA1/2 genetic testing as a companion diagnostic tool to the health insurance coverage is of considerable significance as a spearhead of health insurance medical care for all different types of hereditary tumors. However, several problems related to this companion diagnostic test have emerged, including the estab- lishment of a genetic counseling system and handling of BRCA1/2 genetic tests performed at the patients' own expense. In addition, the purpose of the companion diagnostic test is to confirm drug indication in a case. However, since the test results include the diagnosis of hereditary tumors, there is also an urgent need to improve the medical care system and social environment for family members of patients with pathological mutations. The use of genetic analysis is widespread in the clinical settings, and genetic medical care is anticipated to advance in the future. Therefore, it would be pivotal to come up with measures against hereditary tumors, such as hereditary breast and ovarian cancer(HBOC)syndrome. In this chapter, we describe the current status and prospects of HBOC medical care, with a particular focus on companion diagnostics.


Assuntos
Síndrome Hereditária de Câncer de Mama e Ovário , Feminino , Aconselhamento Genético , Testes Genéticos , Humanos , Japão
16.
J Am Assoc Nurse Pract ; 31(6): 327-329, 2019 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-31181053

RESUMO

Family history risk assessment can identify individuals at increased risk of colorectal cancer (CRC) who would benefit from earlier or more frequent CRC screening. Clinicians should evaluate the patient's family history as well as personal history to identify red flags and patterns that may suggest predisposition to CRC and then use that information to stratify risk into average, increased, and high risk categories to inform genetic counseling recommendations and personalized management.


Assuntos
Neoplasias Colorretais/diagnóstico , Anamnese/métodos , Adulto , Neoplasias Colorretais/genética , Detecção Precoce de Câncer , Feminino , Aconselhamento Genético/métodos , Humanos , Masculino , Pessoa de Meia-Idade
17.
J Am Assoc Nurse Pract ; 31(6): 327-329, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31205282

RESUMO

Family history risk assessment can identify individuals at increased risk of colorectal cancer (CRC) who would benefit from earlier or more frequent CRC screening. Clinicians should evaluate the patient's family history as well as personal history to identify red flags and patterns that may suggest predisposition to CRC and then use that information to stratify risk into average, increased, and high risk categories to inform genetic counseling recommendations and personalized management.


Assuntos
Neoplasias Colorretais/diagnóstico , Anamnese/métodos , Adulto , Neoplasias Colorretais/genética , Detecção Precoce de Câncer , Feminino , Aconselhamento Genético/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Medição de Risco/métodos
18.
Gan To Kagaku Ryoho ; 46(4): 622-625, 2019 Apr.
Artigo em Japonês | MEDLINE | ID: mdl-31164496

RESUMO

In 2018, a total of 11 institutions was selected as the leading hospitals to promote genomic cancer medicine in Japan. In April 2019, a multiplex gene panel test will be approved by government and establishment of infrastructures is now urgently needed in hospitals which implement genomic medicine. Following infrastructures and human resources are relevant to genomic medicine; (1) Education of medical staffs who will be involved in genomic medicine, (2) Medical staffs of pathology department who can properly handle the pathology samples for sequencing tests, (3) Coordinators who assist physicians with gene test application, sample shipping, and appointments of outpatient clinic, (4) Molecular tumor board comprising a variety of medical experts(medical oncologists, pathologists, medical geneticists, bioinformaticians etc), (5) Genetic counseling system for secondary findings. In this section, I would like to introduce how those infrastructures are established in our institution.


Assuntos
Genômica , Neoplasias , Aconselhamento Genético , Humanos , Japão , Neoplasias/genética , Neoplasias/terapia
19.
Einstein (Sao Paulo) ; 17(3): eRC4577, 2019 Jun 13.
Artigo em Inglês, Português | MEDLINE | ID: mdl-31215591

RESUMO

Epidermolysis bullosa describes a group of skin conditions caused by mutations in genes encoding proteins related to dermal-epidermal adhesion. In the United States, 50 cases of epidermolysis bullosa per 1 million live births are estimated, 92% of which classified as simplex, 5% dystrophic, 1% junctional and 2% non-classified. Dystrophic epidermolysis bullosa is associated with autosomal, dominant and recessive inheritance. Epidermolysis bullosa causes severe psychological, economic and social impacts, and there is currently no curative therapy, only symptom control. Embryonic selection is available for epidermolysis bullosa patients in order to prevent perpetuation of the condition in their offspring.


Assuntos
Epidermólise Bolhosa Distrófica/genética , Aconselhamento Genético/métodos , Mutação , Adulto , Colágeno Tipo VII/genética , Feminino , Humanos , Padrões de Herança/genética , Reação em Cadeia da Polimerase
20.
Biomed Res Int ; 2019: 9797104, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31061830

RESUMO

Translocations are the most common type of structural chromosomal abnormalities. Unbalanced translocations are usually found in children who present with congenital abnormalities, developmental delay, or intellectual disability. Balanced translocations are usually found in adults who frequently present with reproductive failure; either subfertility, or recurrent pregnancy loss. Herein, we report the spectrum and frequency of translocations in a Sri Lankan cohort. A database of patients undergoing cytogenetic testing was maintained prospectively from January 2007 to December 2016 and analyzed, retrospectively. A total of 15,864 individuals were tested. Among them, 277 (1.7%) had translocations. There were 142 (51.3%) unbalanced translocations and 135 (48.7%) balanced translocations. Majority (160; 57.8%) were Robertsonian translocations. There were 145 (52.3%) children and adolescents aged less than 18 years with translocations, and 142 (97.9%) were unbalanced translocations. Majority [138 (95.2%)] were referred due to congenital abnormalities, developmental delay, or intellectual disability, and 91 were children with translocation Down syndrome. All adults aged 18 years or above (132) had balanced translocations. Subfertility and recurrent pregnancy loss [84 (63.6%)] and offspring(s) with congenital abnormalities [48 (36.4%)] were the most common indications in this group. Majority (68.2%) in this group were females with reciprocal translocations (55.3%). Chromosomes 21, 14, and 13 were the most commonly involved with rob(14q21q) [72 (26%)], rob(21q21q) [30 (13.7%)], and rob(13q14q) [34 (12.3%)] accounting for 52% of the translocations. Chromosomes 1, 8, 11, and 18 were most commonly involved in reciprocal translocations. The observed high frequency of chromosomal translocations in our cohort highlights the importance of undertaking cytogenetic evaluation and providing appropriate genetic counseling for individuals with the phenotypes associated with these translocations.


Assuntos
Aborto Habitual/genética , Cromossomos Humanos/genética , Síndrome de Down/genética , Translocação Genética , Aborto Habitual/epidemiologia , Adolescente , Adulto , Criança , Pré-Escolar , Síndrome de Down/epidemiologia , Feminino , Aconselhamento Genético , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sri Lanka/epidemiologia
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