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1.
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
2.
Genet Med ; 21(3): 727-735, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-29976988

RESUMO

PURPOSE: In response to genetic testing being widely ordered by nongenetics clinicians, the Consent and Disclosure Recommendations (CADRe) Workgroup of the Clinical Genome Resource (ClinGen; clinicalgenome.org ) developed guidance to facilitate communication about genetic testing and efficiently improve the patient experience. Considering ethical, legal, and social implications, and medical factors, CADRe developed and pilot tested two rubrics addressing consent for genetic testing and results disclosure. The CADRe rubrics allow for adjusting the communication approach based on circumstances specific to patients and ordering clinicians. METHODS: We present results of a formative survey of 66 genetics clinicians to assess the consent rubric for nine genes (MLH1, CDH1, TP53, GJB2, OTC; DMD, HTT, and CYP2C9/VKORC1). We also conducted interviews and focus groups with family and patient stakeholders (N = 18), nongenetics specialists (N = 27), and genetics clinicians (N = 32) on both rubrics. RESULTS: Formative evaluation of the CADRe rubrics suggests key factors on which to make decisions about consent and disclosure discussions for a "typical" patient. CONCLUSION: We propose that the CADRe rubrics include the primary issues necessary to guide communication recommendations, and are ready for pilot testing by nongenetics clinicians. Consultation with genetics clinicians can be targeted toward more complex or intensive consent and disclosure counseling.


Assuntos
Revelação/ética , Aconselhamento Genético/métodos , Pessoal de Saúde/educação , Adulto , Competência Clínica , Comunicação , Confidencialidade , Tomada de Decisões/ética , Feminino , Aconselhamento Genético/normas , Testes Genéticos/ética , Genética/educação , Humanos , Consentimento Livre e Esclarecido/normas , Idioma , Masculino , Estudantes
3.
Hum Mutat ; 39(11): 1668-1676, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30311371

RESUMO

GenomeConnect, the NIH-funded Clinical Genome Resource (ClinGen) patient registry, engages patients in data sharing to support the goal of creating a genomic knowledge base to inform clinical care and research. Participant self-reported health information and genomic variants from genetic testing reports are curated and shared with public databases, such as ClinVar. There are four primary benefits of GenomeConnect: (1) sharing novel genomic data-47.9% of variants were new to ClinVar, highlighting patients as a genomic data source; (2) contributing additional phenotypic information-of the 52.1% of variants already in ClinVar, GenomeConnect provided enhanced case-level data; (3) providing a way for patients to receive variant classification updates if the reporting laboratory submits to ClinVar-97.3% of responding participants opted to receive such information and 13 updates have been identified; and (4) supporting connections with others, including other participants, clinicians, and researchers to enable the exchange of information and support-60.4% of participants have opted to partake in participant matching. Moving forward, ClinGen plans to increase patient-centric data sharing by partnering with other existing patient groups. By engaging patients, more information is contributed to the public knowledge base, benefiting both patients and the genomics community.


Assuntos
Genoma Humano/genética , Genômica/métodos , Disseminação de Informação/métodos , Bases de Dados Genéticas , Testes Genéticos/métodos , Variação Genética , Humanos
4.
Am J Hum Genet ; 103(3): 328-337, 2018 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-30100086

RESUMO

There is growing interest in communicating clinically relevant DNA sequence findings to research participants who join projects with a primary research goal other than the clinical return of such results. Since Geisinger's MyCode Community Health Initiative (MyCode) was launched in 2007, more than 200,000 participants have been broadly consented for discovery research. In 2013 the MyCode consent was amended to include a secondary analysis of research genomic sequences that allows for delivery of clinical results. Since May 2015, pathogenic and likely pathogenic variants from a set list of genes associated with monogenic conditions have prompted "genome-first" clinical encounters. The encounters are described as genome-first because they are identified independent of any clinical parameters. This article (1) details our process for generating clinical results from research data, delivering results to participants and providers, facilitating condition-specific clinical evaluations, and promoting cascade testing of relatives, and (2) summarizes early results and participant uptake. We report on 542 participants who had results uploaded to the electronic health record as of February 1, 2018 and 291 unique clinical providers notified with one or more participant results. Of these 542 participants, 515 (95.0%) were reached to disclose their results and 27 (5.0%) were lost to follow-up. We describe an exportable model for delivery of clinical care through secondary use of research data. In addition, subject and provider participation data from the initial phase of these efforts can inform other institutions planning similar programs.


Assuntos
Genoma Humano/genética , Estudos de Coortes , Registros Eletrônicos de Saúde , Genômica/métodos , Pessoal de Saúde , Humanos , Análise de Sequência de DNA/métodos
5.
Health Aff (Millwood) ; 37(5): 757-764, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29733722

RESUMO

Health care delivery is increasingly influenced by the emerging concepts of precision health and the learning health care system. Although not synonymous with precision health, genomics is a key enabler of individualized care. Delivering patient-centered, genomics-informed care based on individual-level data in the current national landscape of health care delivery is a daunting challenge. Problems to overcome include data generation, analysis, storage, and transfer; knowledge management and representation for patients and providers at the point of care; process management; and outcomes definition, collection, and analysis. Development, testing, and implementation of a genomics-informed program requires multidisciplinary collaboration and building the concepts of precision health into a multilevel implementation framework. Using the principles of a learning health care system provides a promising solution. This article describes the implementation of population-based genomic medicine in an integrated learning health care system-a working example of a precision health program.


Assuntos
Prestação Integrada de Cuidados de Saúde/organização & administração , Genômica , Assistência Centrada no Paciente/organização & administração , Medicina de Precisão , Feminino , Humanos , Aprendizagem , Masculino , Desenvolvimento de Programas , Avaliação de Programas e Projetos de Saúde , Estados Unidos
6.
JAMA Netw Open ; 1(5): e182140, 2018 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-30646163

RESUMO

Importance: Detection of disease-associated variants in the BRCA1 and BRCA2 (BRCA1/2) genes allows for cancer prevention and early diagnosis in high-risk individuals. Objectives: To identify pathogenic and likely pathogenic (P/LP) BRCA1/2 variants in an unselected research cohort, and to characterize the features associated with P/LP variants. Design, Setting, and Participants: This is a cross-sectional study of adult volunteers (n = 50 726) who underwent exome sequencing at a single health care system (Geisinger Health System, Danville, Pennsylvania) from January 1, 2014, to March 1, 2016. Participants are part of the DiscovEHR cohort and were identified through the Geisinger MyCode Community Health Initiative. They consented to a research protocol that included sequencing and return of actionable test results. Clinical data from electronic health records and clinical visits were correlated with variants. Comparisons were made between those with (cases) and those without (controls) P/LP variants in BRCA1/2. Main Outcomes: Prevalence of P/LP BRCA1/2 variants in cohort, proportion of variant carriers not previously ascertained through clinical testing, and personal and family history of relevant cancers among BRCA1/2 variant carriers and noncarriers. Results: Of the 50 726 health system patients who underwent exome sequencing, 50 459 (99.5%) had no expected pathogenic BRCA1/2 variants and 267 (0.5%) were BRCA1/2 carriers. Of the 267 cases (148 [55.4%] were women and 119 [44.6%] were men with a mean [range] age of 58.9 [23-90] years), 183 (68.5%) received clinically confirmed results in their electronic health record. Among the 267 participants with P/LP BRCA1/2 variants, 219 (82.0%) had no prior clinical testing, 95 (35.6%) had BRCA1 variants, and 172 (64.4%) had BRCA2 variants. Syndromic cancer diagnoses were present in 11 (47.8%) of the 23 deceased BRCA1/2 carriers and in 56 (20.9%) of all 267 BRCA1/2 carriers. Among women, 31 (20.9%) of 148 variant carriers had a personal history of breast cancer, compared with 1554 (5.2%) of 29 880 noncarriers (odds ratio [OR], 5.95; 95% CI, 3.88-9.13; P < .001). Ovarian cancer history was present in 15 (10.1%) of 148 variant carriers and in 195 (0.6%) of 29 880 variant noncarriers (OR, 18.30; 95% CI, 10.48-31.4; P < .001). Among 89 BRCA1/2 carriers without prior testing but with comprehensive personal and family history data, 44 (49.4%) did not meet published guidelines for clinical testing. Conclusions and Relevance: This study found that compared with previous clinical care, exome sequencing-based screening identified 5 times as many individuals with P/LP BRCA1/2 variants. These findings suggest that genomic screening may identify BRCA1/2-associated cancer risk that might otherwise remain undetected within health care systems and may provide opportunities to reduce morbidity and mortality in patients.


Assuntos
Proteína BRCA1/análise , Proteína BRCA2/análise , Sequenciamento Completo do Exoma/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteína BRCA1/genética , Proteína BRCA2/genética , Bancos de Espécimes Biológicos/estatística & dados numéricos , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/sangue , Estudos Transversais , Detecção Precoce de Câncer/métodos , Exoma/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pennsylvania , Virulência/genética , Sequenciamento Completo do Exoma/estatística & dados numéricos
7.
Genet Med ; 20(5): 554-558, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29261187

RESUMO

PurposeThe clinical utility of screening unselected individuals for pathogenic BRCA1/2 variants has not been established. Data on cancer risk management behaviors and diagnoses of BRCA1/2-associated cancers can help inform assessments of clinical utility.MethodsWhole-exome sequences of participants in the MyCode Community Health Initiative were reviewed for pathogenic/likely pathogenic BRCA1/2 variants. Clinically confirmed variants were disclosed to patient-participants and their clinicians. We queried patient-participants' electronic health records for BRCA1/2-associated cancer diagnoses and risk management that occurred within 12 months after results disclosure, and calculated the percentage of patient-participants of eligible age who had begun risk management.ResultsThirty-seven MyCode patient-participants were unaware of their pathogenic/likely pathogenic BRCA1/2 variant, had not had a BRCA1/2-associated cancer, and had 12 months of follow-up. Of the 33 who were of an age to begin BRCA1/2-associated risk management, 26 (79%) had performed at least one such procedure. Three were diagnosed with an early-stage, BRCA1/2-associated cancer-including a stage 1C fallopian tube cancer-via these procedures.ConclusionScreening for pathogenic BRCA1/2 variants among unselected individuals can lead to occult cancer detection shortly after disclosure. Comprehensive outcomes data generated within our learning healthcare system will aid in determining whether population-wide BRCA1/2 genomic screening programs offer clinical utility.


Assuntos
Bancos de Espécimes Biológicos , Detecção Precoce de Câncer/métodos , Genes BRCA1 , Genes BRCA2 , Mutação , Neoplasias/diagnóstico , Neoplasias/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Associação Genética , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Síndrome Hereditária de Câncer de Mama e Ovário/diagnóstico , Síndrome Hereditária de Câncer de Mama e Ovário/genética , Humanos , Pessoa de Meia-Idade , Linhagem , Sequenciamento Completo do Genoma
8.
J Genet Couns ; 27(2): 470-480, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29130143

RESUMO

Patients with newly-described or rare genetic findings are turning to social media to find and connect with others. Blogs, Facebook groups, and Twitter have all been reported as tools for patients to connect with one another. However, the preferences for social media use and privacy among patients, their families, and these communities have not been well characterized. To explore preferences about privacy and membership guidelines, an online survey was administered to two web-based patient registries, Simons Variation in Individuals Project ( www.simonsvipconnect.org ) and GenomeConnect ( www.genomeconnect.org ). Over a three-month period, invitations were sent to 2524 individuals and 103 responses (4%) were received and analyzed. Responses indicate that Facebook is the most popular resource accessed within this sample population (99%). Participants used social media to look for information about their diagnosis or test results (83%), read posts from rare disease groups or organizations (73%), participate in conversations about their diagnosis (67%), and connect with others to find support (58%). Focusing on privacy issues in social media, respondents indicate that membership and access impact the level of comfort in sharing personal or medical information. Nearly 60% of respondents felt uncomfortable sharing photos or medical information within a public Facebook group, whereas only 12% of respondents felt uncomfortable sharing in private group targeted to families alone. Using this preliminary data concerning social media use and privacy, we developed points for genetic counselors to incorporate when discussing available support resources for patients with a new, or rare, genetic diagnosis or genetic test result. Genetic counselors are trained to provide anticipatory guidance to families adapting to new genetic information, and are well-equipped to help patients consider their preferences about using social media as a source of information and support.


Assuntos
Aconselhamento Genético , Mídias Sociais , Apoio Social , Feminino , Humanos , Masculino , Inquéritos e Questionários
9.
Am J Hum Genet ; 101(2): 167-176, 2017 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-28777929

RESUMO

With CRISPR/Cas9 and other genome-editing technologies, successful somatic and germline genome editing are becoming feasible. To respond, an American Society of Human Genetics (ASHG) workgroup developed this position statement, which was approved by the ASHG Board in March 2017. The workgroup included representatives from the UK Association of Genetic Nurses and Counsellors, Canadian Association of Genetic Counsellors, International Genetic Epidemiology Society, and US National Society of Genetic Counselors. These groups, as well as the American Society for Reproductive Medicine, Asia Pacific Society of Human Genetics, British Society for Genetic Medicine, Human Genetics Society of Australasia, Professional Society of Genetic Counselors in Asia, and Southern African Society for Human Genetics, endorsed the final statement. The statement includes the following positions. (1) At this time, given the nature and number of unanswered scientific, ethical, and policy questions, it is inappropriate to perform germline gene editing that culminates in human pregnancy. (2) Currently, there is no reason to prohibit in vitro germline genome editing on human embryos and gametes, with appropriate oversight and consent from donors, to facilitate research on the possible future clinical applications of gene editing. There should be no prohibition on making public funds available to support this research. (3) Future clinical application of human germline genome editing should not proceed unless, at a minimum, there is (a) a compelling medical rationale, (b) an evidence base that supports its clinical use, (c) an ethical justification, and (d) a transparent public process to solicit and incorporate stakeholder input.


Assuntos
Edição de Genes , Genoma Humano/genética , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas/genética , Edição de Genes/ética , Edição de Genes/legislação & jurisprudência , Edição de Genes/métodos , Humanos , Mudança Social
11.
Expert Rev Mol Diagn ; 16(5): 521-32, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26810587

RESUMO

Precision or personalized medicine through clinical genome and exome sequencing has been described by some as a revolution that could transform healthcare delivery, yet it is currently used in only a small fraction of patients, principally for the diagnosis of suspected Mendelian conditions and for targeting cancer treatments. Given the burden of illness in our society, it is of interest to ask how clinical genome and exome sequencing can be constructively integrated more broadly into the routine practice of medicine for the betterment of public health. In November 2014, 46 experts from academia, industry, policy and patient advocacy gathered in a conference sponsored by Illumina, Inc. to discuss this question, share viewpoints and propose recommendations. This perspective summarizes that work and identifies some of the obstacles and opportunities that must be considered in translating advances in genomics more widely into the practice of medicine.


Assuntos
Assistência à Saúde/organização & administração , Genoma Humano , Genômica/métodos , Medicina de Precisão/tendências , Assistência à Saúde/métodos , Testes Genéticos , Genômica/instrumentação , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Kit de Reagentes para Diagnóstico
12.
JAMA Psychiatry ; 73(1): 20-30, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26629640

RESUMO

IMPORTANCE: The 16p11.2 BP4-BP5 duplication is the copy number variant most frequently associated with autism spectrum disorder (ASD), schizophrenia, and comorbidities such as decreased body mass index (BMI). OBJECTIVES: To characterize the effects of the 16p11.2 duplication on cognitive, behavioral, medical, and anthropometric traits and to understand the specificity of these effects by systematically comparing results in duplication carriers and reciprocal deletion carriers, who are also at risk for ASD. DESIGN, SETTING, AND PARTICIPANTS: This international cohort study of 1006 study participants compared 270 duplication carriers with their 102 intrafamilial control individuals, 390 reciprocal deletion carriers, and 244 deletion controls from European and North American cohorts. Data were collected from August 1, 2010, to May 31, 2015 and analyzed from January 1 to August 14, 2015. Linear mixed models were used to estimate the effect of the duplication and deletion on clinical traits by comparison with noncarrier relatives. MAIN OUTCOMES AND MEASURES: Findings on the Full-Scale IQ (FSIQ), Nonverbal IQ, and Verbal IQ; the presence of ASD or other DSM-IV diagnoses; BMI; head circumference; and medical data. RESULTS: Among the 1006 study participants, the duplication was associated with a mean FSIQ score that was lower by 26.3 points between proband carriers and noncarrier relatives and a lower mean FSIQ score (16.2-11.4 points) in nonproband carriers. The mean overall effect of the deletion was similar (-22.1 points; P < .001). However, broad variation in FSIQ was found, with a 19.4- and 2.0-fold increase in the proportion of FSIQ scores that were very low (≤40) and higher than the mean (>100) compared with the deletion group (P < .001). Parental FSIQ predicted part of this variation (approximately 36.0% in hereditary probands). Although the frequency of ASD was similar in deletion and duplication proband carriers (16.0% and 20.0%, respectively), the FSIQ was significantly lower (by 26.3 points) in the duplication probands with ASD. There also were lower head circumference and BMI measurements among duplication carriers, which is consistent with the findings of previous studies. CONCLUSIONS AND RELEVANCE: The mean effect of the duplication on cognition is similar to that of the reciprocal deletion, but the variance in the duplication is significantly higher, with severe and mild subgroups not observed with the deletion. These results suggest that additional genetic and familial factors contribute to this variability. Additional studies will be necessary to characterize the predictors of cognitive deficits.


Assuntos
Transtorno do Espectro Autista/psicologia , Transtorno Autístico/psicologia , Transtornos Cromossômicos/psicologia , Duplicação Cromossômica , Cromossomos Humanos Par 16/genética , Cognição , Deficiência Intelectual/psicologia , Esquizofrenia/genética , Adolescente , Adulto , Transtorno do Espectro Autista/epidemiologia , Transtorno do Espectro Autista/genética , Transtorno Autístico/epidemiologia , Transtorno Autístico/genética , Estudos de Casos e Controles , Cerebelo/anormalidades , Criança , Pré-Escolar , Deleção Cromossômica , Transtornos Cromossômicos/epidemiologia , Transtornos Cromossômicos/genética , Estudos de Coortes , Comorbidade , Variações do Número de Cópias de DNA , Deficiências do Desenvolvimento/epidemiologia , Deficiências do Desenvolvimento/genética , Epilepsia/epidemiologia , Epilepsia/genética , Feminino , Humanos , Deficiência Intelectual/epidemiologia , Deficiência Intelectual/genética , Masculino , Microcefalia/epidemiologia , Microcefalia/genética , Pessoa de Meia-Idade , Malformações do Sistema Nervoso/epidemiologia , Malformações do Sistema Nervoso/genética , Esquizofrenia/epidemiologia , Psicologia do Esquizofrênico , Adulto Jovem
13.
Hum Mutat ; 36(10): 974-8, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26178529

RESUMO

As the utility of genetic and genomic testing in healthcare grows, there is need for a high-quality genomic knowledge base to improve the clinical interpretation of genomic variants. Active patient engagement can enhance communication between clinicians, patients, and researchers, contributing to knowledge building. It also encourages data sharing by patients and increases the data available for clinicians to incorporate into individualized patient care, clinical laboratories to utilize in test interpretation, and investigators to use for research. GenomeConnect is a patient portal supported by the Clinical Genome Resource (ClinGen), providing an opportunity for patients to add to the knowledge base by securely sharing their health history and genetic test results. Data can be matched with queries from clinicians, laboratory personnel, and researchers to better interpret the results of genetic testing and build a foundation to support genomic medicine. Participation is online, allowing patients to contribute regardless of location. GenomeConnect supports longitudinal, detailed clinical phenotyping and robust "matching" among research and clinical communities. Phenotype data are gathered using online health questionnaires; genotype data are obtained from genetic test reports uploaded by participants and curated by staff. GenomeConnect empowers patients to actively participate in the improvement of genomic test interpretation and clinical utility.


Assuntos
Bases de Dados Factuais , Doença/genética , Disseminação de Informação/métodos , Predisposição Genética para Doença , Genoma Humano , Humanos , Participação do Paciente , Fenótipo , Medicina de Precisão , Interface Usuário-Computador
14.
JAMA Psychiatry ; 72(2): 119-26, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25493922

RESUMO

IMPORTANCE: Most disorders caused by copy number variants (CNVs) display significant clinical variability, often referred to as incomplete penetrance and variable expressivity. Genetic and environmental sources of this variability are not well understood. OBJECTIVES: To investigate the contributors to phenotypic variability in probands with CNVs involving the same genomic region; to measure the effect size for de novo mutation events; and to explore the contribution of familial background to resulting cognitive, behavioral, and motor performance outcomes in probands with de novo CNVs. DESIGN, SETTING, AND PARTICIPANTS: Family-based study design with a volunteer sample of 56 individuals with de novo 16p11.2 deletions and their noncarrier parents and siblings from the Simons Variation in Individuals Project. MAIN OUTCOMES AND MEASURES: We used linear mixed-model analysis to measure effect size and intraclass correlation to determine the influence of family background for a de novo CNV on quantitative traits representing the following 3 neurodevelopmental domains: cognitive ability (Full-Scale IQ), social behavior (Social Responsiveness Scale), and neuromotor performance (Purdue Pegboard Test). We included an anthropometric trait, body mass index, for comparison. RESULTS: A significant deleterious effect of the 16p11.2 deletion was demonstrated across all domains. Relative to the biparental mean, the effect sizes were -1.7 SD for cognitive ability, 2.2 SD for social behavior, and -1.3 SD for neuromotor performance (P < .001). Despite large deleterious effects, significant positive correlations between parents and probands were preserved for the Full-Scale IQ (0.42 [P = .03]), the verbal IQ (0.53 [P = .004]), and the Social Responsiveness Scale (0.52 [P = .009]) scores. We also observed a 1-SD increase in the body mass index of probands compared with siblings, with an intraclass correlation of 0.40 (P = .07). CONCLUSIONS AND RELEVANCE: Analysis of families with de novo CNVs provides the least confounded estimate of the effect size of the 16p11.2 deletion on heritable, quantitative traits and demonstrates a 1- to 2-SD effect across all neurodevelopmental dimensions. Significant parent-proband correlations indicate that family background contributes to the phenotypic variability seen in this and perhaps other CNV disorders and may have implications for counseling families regarding their children's developmental and psychiatric prognoses. Use of biparental mean scores rather than general population mean scores may be more relevant to examine the effect of a mutation or any other cause of trait variation on a neurodevelopmental outcome and possibly on systems of diagnosis and trait ascertainment for developmental disorders.


Assuntos
Transtorno Autístico/fisiopatologia , Transtornos Cromossômicos/fisiopatologia , Deficiência Intelectual/fisiopatologia , Inteligência/genética , Pais , Fenótipo , Desempenho Psicomotor/fisiologia , Comportamento Social , Adulto , Transtorno Autístico/genética , Deleção Cromossômica , Transtornos Cromossômicos/genética , Cromossomos Humanos Par 16/genética , Variações do Número de Cópias de DNA/genética , Feminino , Humanos , Deficiência Intelectual/genética , Masculino , Irmãos
15.
J Genet Couns ; 23(6): 938-47, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24569858

RESUMO

Because of the higher yield over traditional chromosomal analysis, chromosomal microarray analysis (CMA) is being used increasingly in prenatal diagnosis. Unfortunately, the clinical implication of many copy number variants found on prenatal CMA is uncertain, complicating genetic counseling. Recognizing that uncertain results will be encountered frequently as more of the genome is assayed prenatally, we set out to understand the experiences and needs of genetic counselors when counseling patients about uncertain prenatal microarray results, their comfort with various aspects of prenatal genetic counseling, and their interest in additional education and training about prenatal microarray testing. We first interviewed 10 genetic counselors about their experiences of providing pre- and post-test genetic counseling about prenatal CMA. Based on the findings from the counselor interviews, we developed items for a survey to assess the prevalence of genetic counselors' attitudes towards, experience and comfort with, and educational needs regarding prenatal CMA. Based on surveys completed by 193 prenatal genetic counselors, we found that when there is an uncertain CMA result, only 59% would be comfortable providing genetic counseling and only 43% would be comfortable helping a patient make a decision about pregnancy termination. Being less comfortable was associated with seeing fewer patients having prenatal CMA testing. Respondents expressed a high degree of interest in additional education about prenatal CMA and counseling about uncertain results. Further genetic counselor education and training aimed at improving counselors' personal comfort with uncertain results and communicating about them with patients is needed.


Assuntos
Atitude do Pessoal de Saúde , Aberrações Cromossômicas , Aconselhamento Genético/métodos , Testes Genéticos/métodos , Diagnóstico Pré-Natal/métodos , Adulto , Feminino , Aconselhamento Genético/psicologia , Humanos , Análise em Microsséries/métodos , Gravidez
16.
J Genet Couns ; 23(4): 516-21, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24573557

RESUMO

Whole genome sequencing (WGS) is being used for evaluation of individuals with undiagnosed disease of suspected genetic origin. Implementing WGS into clinical practice will place an increased burden upon care teams with regard to pre-test patient education and counseling about results. To quantitate the time needed for appropriate pre-test evaluation of participants in WGS testing, we documented the time spent by our clinical research group on various activities related to program preparation, participant screening, and consent prior to WGS. Participants were children or young adults with autism, intellectual or developmental disability, and/or congenital anomalies, who have remained undiagnosed despite previous evaluation, and their biologic parents. Results showed that significant time was spent in securing allocation of clinical research space to counsel participants and families, and in acquisition and review of participant's medical records. Pre-enrollment chart review identified two individuals with existing diagnoses resulting in savings of $30,000 for the genome sequencing alone, as well as saving hours of personnel time for genome interpretation and communication of WGS results. New WGS programs should plan for costs associated with additional pre-test administrative planning and patient evaluation time that will be required to provide high quality care.


Assuntos
Aconselhamento Genético , Humanos , Análise de Sequência
17.
Genet Med ; 15(10): 761-71, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23743551

RESUMO

The Electronic Medical Records and Genomics Network is a National Human Genome Research Institute-funded consortium engaged in the development of methods and best practices for using the electronic medical record as a tool for genomic research. Now in its sixth year and second funding cycle, and comprising nine research groups and a coordinating center, the network has played a major role in validating the concept that clinical data derived from electronic medical records can be used successfully for genomic research. Current work is advancing knowledge in multiple disciplines at the intersection of genomics and health-care informatics, particularly for electronic phenotyping, genome-wide association studies, genomic medicine implementation, and the ethical and regulatory issues associated with genomics research and returning results to study participants. Here, we describe the evolution, accomplishments, opportunities, and challenges of the network from its inception as a five-group consortium focused on genotype-phenotype associations for genomic discovery to its current form as a nine-group consortium pivoting toward the implementation of genomic medicine.


Assuntos
Registros Eletrônicos de Saúde , Pesquisa em Genética , Genômica , Registros Eletrônicos de Saúde/tendências , Pesquisa em Genética/ética , Estudo de Associação Genômica Ampla , Genômica/ética , Genômica/tendências , Genótipo , Humanos , National Human Genome Research Institute (U.S.) , Fenótipo , Medicina de Precisão , Estados Unidos
18.
Hum Mutat ; 34(6): 915-9, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23463607

RESUMO

The 2012 International Standards for Cytogenomic Arrays (ISCA) Consortium Meeting, "Towards a Universal Clinical Genomic Database," was held in Bethesda, Maryland, May 21-22, 2012, and was attended by over 200 individuals from around the world representing clinical genetic testing laboratories, clinicians, academia, industry, research, and regulatory agencies. The scientific program centered on expanding the current focus of the ISCA Consortium to include the collection and curation of both structural and sequence-level variation into a unified clinical genomics database, available to the public through resources such as the National Center for Biotechnology Information's ClinVar database. Here, we provide an overview of the conference, with summaries of the topics presented for discussion by over 25 different speakers. Presentations are available online at www.iscaconsortium.org.


Assuntos
Bases de Dados Genéticas , Genômica , Humanos
19.
J Med Genet ; 49(10): 660-8, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23054248

RESUMO

BACKGROUND: The recurrent ~600 kb 16p11.2 BP4-BP5 deletion is among the most frequent known genetic aetiologies of autism spectrum disorder (ASD) and related neurodevelopmental disorders. OBJECTIVE: To define the medical, neuropsychological, and behavioural phenotypes in carriers of this deletion. METHODS: We collected clinical data on 285 deletion carriers and performed detailed evaluations on 72 carriers and 68 intrafamilial non-carrier controls. RESULTS: When compared to intrafamilial controls, full scale intelligence quotient (FSIQ) is two standard deviations lower in carriers, and there is no difference between carriers referred for neurodevelopmental disorders and carriers identified through cascade family testing. Verbal IQ (mean 74) is lower than non-verbal IQ (mean 83) and a majority of carriers require speech therapy. Over 80% of individuals exhibit psychiatric disorders including ASD, which is present in 15% of the paediatric carriers. Increase in head circumference (HC) during infancy is similar to the HC and brain growth patterns observed in idiopathic ASD. Obesity, a major comorbidity present in 50% of the carriers by the age of 7 years, does not correlate with FSIQ or any behavioural trait. Seizures are present in 24% of carriers and occur independently of other symptoms. Malformations are infrequently found, confirming only a few of the previously reported associations. CONCLUSIONS: The 16p11.2 deletion impacts in a quantitative and independent manner FSIQ, behaviour and body mass index, possibly through direct influences on neural circuitry. Although non-specific, these features are clinically significant and reproducible. Lastly, this study demonstrates the necessity of studying large patient cohorts ascertained through multiple methods to characterise the clinical consequences of rare variants involved in common diseases.


Assuntos
Transtornos Globais do Desenvolvimento Infantil/genética , Deleção Cromossômica , Cromossomos Humanos Par 16 , Deficiências do Desenvolvimento/genética , Fenótipo , Adolescente , Adulto , Índice de Massa Corporal , Criança , Transtornos Globais do Desenvolvimento Infantil/diagnóstico , Deficiências do Desenvolvimento/diagnóstico , Feminino , Ordem dos Genes , Heterozigoto , Humanos , Testes de Inteligência , Masculino , Síndrome , Adulto Jovem
20.
J Genet Couns ; 21(5): 631-7, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22610653

RESUMO

The International Standards for Cytogenomic Arrays (ISCA) Consortium is a worldwide collaborative effort dedicated to optimizing patient care by improving the quality of chromosomal microarray testing. The primary effort of the ISCA Consortium has been the development of a database of copy number variants (CNVs) identified during the course of clinical microarray testing. This database is a powerful resource for clinicians, laboratories, and researchers, and can be utilized for a variety of applications, such as facilitating standardized interpretations of certain CNVs across laboratories or providing phenotypic information for counseling purposes when published data is sparse. A recognized limitation to the clinical utility of this database, however, is the quality of clinical information available for each patient. Clinical genetic counselors are uniquely suited to facilitate the communication of this information to the laboratory by virtue of their existing clinical responsibilities, case management skills, and appreciation of the evolving nature of scientific knowledge. We intend to highlight the critical role that genetic counselors play in ensuring optimal patient care through contributing to the clinical utility of the ISCA Consortium's database, as well as the quality of individual patient microarray reports provided by contributing laboratories. Current tools, paper and electronic forms, created to maximize this collaboration are shared. In addition to making a professional commitment to providing complete clinical information, genetic counselors are invited to become ISCA members and to become involved in the discussions and initiatives within the Consortium.


Assuntos
Aberrações Cromossômicas , Comunicação , Comportamento Cooperativo , Pessoal de Laboratório , Equipe de Assistência ao Paciente , Assistência ao Paciente , Humanos , Análise de Sequência com Séries de Oligonucleotídeos , Fenótipo
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