Limitations Of Genetic Testing Research Articles

Genetics in clinical epilepsy: Issues in genetic testing and counseling

In the last decade, major advances have been made in our understanding of the genetic basis of epilepsy. Genetic testing for over two dozen epilepsy-related genes is now clinically available, and healthcare providers who manage patients with epilepsy are faced with incorporating genetic information into their assessment and treatment plans. Although the clinical applications of genetic test results in the setting of epilepsy may be somewhat limited, an argument for the utility of testing can be made based upon the potential impact on treatment options, the ability to provide prognostic information, and the psychological, medical, and reproductive implications for patients and their family members. Clinicians who incorporate genetic testing into their evalua- tion of patients with epilepsy must be knowledgeable about epilepsy phenotypes and epilepsy genes, have expertise in eliciting a genetic family history that encompasses not only epilepsy but a broader range of relevant medical conditions, and possess a thor- ough understanding of genetic testing methods and outcomes. Given the complexity of genetic test results, it is crucial that informed consent to discuss the risks, benefits, and limitations of genetic testing take place with patients prior to testing. In addi- tion, many patients may benefit from genetic counseling to discuss testing options or results, address family impact or reproductive issues, and obtain access to support resources.

Identifying hereditary cancer: Genetic counseling and cancer risk assessment

The goal of cancer genetic counseling, risk assessment, and testing is to identify individuals and families at risk for hereditary cancer, such that targeted management strategies can be used to reduce associated morbidity and mortality. Involvement of a qualified cancer genetic service provider helps to ensure that at-risk individuals identified and offered appropriate education, risk assessment, genetic testing, and follow-up risk management strategies. There are multiple screening and hereditary risk models available to help the clinician identify who needs to be referred to cancer genetic counseling and to facilitate the cancer risk assessment process. Genetic testing should only be pursued with fully informed consent in the context of pretest counseling to ensure that the individual understands the benefits, risks, and limitations of genetic testing, possible results, and their implications. Incorporating psychosocial assessment throughout the counseling session may assist the individual in their understanding of genetic testing in the context of their support resources and coping mechanisms and may help with decision making. There is a growing public awareness of and interest in cancer genetic testing, as well as increasing complexity of available testing options and results. It is therefore essential that cancer genetic professionals, primary care providers, and oncology practitioners work together to ensure that genetic testing for hereditary cancer syndromes is used in the most appropriate and effective way.

Effectiveness of the Interventions Utilized in Genetic Counseling

Background. Advances in genetic science and biotechnology accumulated huge knowledge of genes and various genetic tests and diagnostic tools for healthcare providers including nurses. Genetic counseling became important to assist patients making decisions about obtaining genetic testing or preventive measures. Method. This review was conducted to describe the counseling topics, various interventions adopted in genetic counseling, and their effectiveness. Experimental studies (N=39) published between 1999 and 2012 were synthesized. Results. The most frequently covered topic was benefits and limitations of genetic testing on breast cancer ovarian and colorectal cancers. Most of researchers focused on evaluating cognitive aspect and psychological well-being. Conclusion. No single intervention was consistently reported to be effective. Decision aids enhanced with information technologies have potential to improve the outcomes of genetic counseling by providing tailored information and facilitating active engagement of patients in information uptake. Clinical Implication. When nurses are familiar with topics and interventions of genetic counseling, they are well positioned to provide genetic/genomic information to the patient and families.

Genetic services and attitudes in primary care pediatrics

Given the integral role primary care pediatricians (PCPs) play in caring for children with genetic conditions, we aimed to identify current practices of PCPs regarding genetic patients, their attitudes toward genetic medical care and their choices regarding family history taking. We conducted an on-line survey of a national convenience sample of PCPs associated with the American Academy of Pediatrics' Quality Improvement Innovation Networks. Eighty-eight respondents (29% response rate) were included in the analysis. Seventy-four (86%) reported ordering genetic based tests three or less times annually. Eleven (13%) strongly agreed that they discuss with patients the potential risks, benefits, and limitations of genetic tests. Forty-three (49%) agreed or strongly agreed that they feel competent in providing healthcare to patients related to genetics and genomics. Perceived competence was not associated with more recent training (P = 0.29), number of genetic tests ordered annually (P = 0.84) or mean number of weekly patient encounters (P = 0.15). 100% of participants stated that taking a family history is important. 27 (31%) agreed or strongly agreed that they gather a minimum of a three-generation family history. Forty-one of the 63 participants with an electronic health record (65%) reported their system was fair or poor in its ability to easily capture a three-generation family history. PCPs interested in quality improvement reported variation in care practices for children with genetic diseases and a majority did not feel competent to provide genetic related healthcare. Research should focus on improving the care and diagnosis of children with genetic disorders and enhanced integration of genetic medicine into routine primary preventative care.

Genetic testing of LRRK2 in Parkinson's disease: is there a clinical role?

Genetic testing has played an important role for the diagnosis of many rare monogenic disorders. However, the role and limitations of genetic testing have generated considerable debate in the medical community. In recent years, the identification of several monogenic genes in Parkinson's disease (PD), a common neurodegenerative disorder, has led to calls for genetic testing guidelines for this disorder. Genetic testing of LRRK2 provides an excellent platform to highlight some of the pertinent issues (generic and specific) related to genetic testing in PD. The identification of a common recurrent mutation (G2019S) worldwide provides an opportunity for developing guidelines that are applicable internationally. However, the incomplete penetrance of the mutation and the lack of clarity of the pathogenicity of many other reported LRRK2 mutations call for cautious implementation of genetic testing programs. The clinical utility of genetic testing is compounded by easy accessibility of Direct to Consumer genetic services and the relative lack of regulation on reliability of service providers in internet advertisements. Based on current literature, genetic testing of LRRK2 (particularly for G2019S) certainly has a clinical role, though it is applicable primarily in select scenarios and in certain at-risk populations.

Performance of in silico analysis in predicting the effect of non-synonymous variants in inherited steroid metabolic diseases

BackgroundUnclassified genetic variants are commonly encountered in molecular diagnostic service. In silico analyses using web-based predictive programs may provide information on the nature of the genetic variants, and help to prioritize novel variants for in vitro functional characterization. The objective of this study was to compare the performance of three such programs in genes related to steroid metabolism. MethodsThe effects of non-synonymous benign and pathogenic sequence variants in the CYP11A1, CYP11B1, CYP11B2, CYP17A1, CYP19A1, CYP21A2, DHCR7, HSD3B2, HSD11B2, HSD17B3, POR, and SRD5A2 genes listed in the Human Gene Mutation Database and dbSNP were tested by SIFT, PolyPhen-2 and PON-P. Their concordance, sensitivity, specificity, positive and negative predictive values and accuracy were assessed, using the reported phenotype and the in vitro functional data as gold standards. Results797 sequence variants were tested. SIFT and PolyPhen-2 had high concordance, with PolyPhen-2 being slightly superior to SIFT in all assessments. PON-P behaved differently, with one-third of the variants unclassified. ConclusionsSIFT and PolyPhen-2 behaved similarly while PON-P behaved differently in predicting pathogenicity in genes related to steroid metabolism. Molecular pathologists should verify the performance of these programs before considering them in clinical decision making, and be aware that these programmes cannot replace in vitro function studies. Clinicians and patients should also be informed about the limitations of genetic testing, particularly when a novel variant is encountered.

Public knowledge of and attitudes toward genetics and genetic testing.

Variable health literacy and genetic knowledge may pose significant challenges to engaging the general public in personal genomics, specifically with respect to promoting risk comprehension and healthy behaviors. We are conducting a multistage study of individual responses to genomic risk information for Type 2 diabetes mellitus. A total of 300 individuals were recruited from the general public in Durham, North Carolina: 60% self-identified as White; 70% female; and 65% have a college degree. As part of the baseline survey, we assessed genetic knowledge and attitudes toward genetic testing. Scores of factual knowledge of genetics ranged from 50% to 100% (average=84%), with significant differences in relation to racial groups, the education level, and age. Scores were significantly higher on questions pertaining to the inheritance and causes of disease (mean score 90%) compared to scientific questions (mean score 77.4%). Scores on the knowledge survey were significantly higher than scores from European populations. Participants' perceived knowledge of the social consequences of genetic testing was significantly lower than their perceived knowledge of the medical uses of testing. More than half agreed with the statement that testing may affect a person's ability to obtain health insurance (51.3%) and 16% were worried about the consequences of testing for chances of finding a job. Despite the relatively high educational status and genetic knowledge of the study population, we find an imbalance of knowledge between scientific and medical concepts related to genetics as well as between the medical applications and societal consequences of testing, suggesting that more effort is needed to present the benefits, risks, and limitations of genetic testing, particularly, at the social and personal levels, to ensure informed decision making.

Genetic evaluation procedures at sperm banks in the United States

To assess how genetic evaluations of sperm donor applicants are performed in the United States. A questionnaire was designed to assess: 1) the professionals involved in the family history evaluation and genetic screening; 2) the genetic testing, counseling, and informed consent processes; and 3) how the results of genetic evaluations and new risk information is communicated to donors. Semen donor facilities. Representatives of semen donor facilities. None. Descriptive data. Thirteen responses were received. All of the facilities assessed donors' family histories; eight of the facilities (62%) routinely informed donors about the results of these evaluations. At the majority of facilities (10/13), informed consent for genetic testing is obtained as part of the overall contract to be a sperm donor. Genetic counselors are employed full-time at two facilities and part-time at five others. There is variability in the education and informed consent processes for semen donor applicants, including variable communication about the limitations of genetic tests and the potential implications for the donors' own children. Further research into the best practices for education and consent for sperm donor applicants may be beneficial to ensure the well-being of the donors and their future offspring.

Pretest genetic counseling informs patients withBRCAmutation

When patients with breast cancer received pretest genetic counseling before undergoing definitive surgery for breast cancer, they showed fewer signs of distress. At the same time, patients who were offered counseling after surgery improved their informed decision-making, while both groups were better informed, according to a study by researchers at the H. Lee Moffitt Cancer Center and Research Institute in Tampa, Florida. The study, funded by the American Cancer Society, was published in the Annals of Surgical Oncology.1 The researchers note that patients with breast cancer with certain risk factors likely would benefit from pretest genetic counseling and genetic testing at or near the time of their initial diagnosis. Although some health care providers may fear that these efforts could increase distress for patients at this time, few studies to date have actually examined the impact of such pretest genetic counseling, according to lead coauthor Susan Vadaparampil, PhD, MPH, an associate member of the Health Outcomes and Behavior Program at H. Lee Moffitt. She and her colleagues developed a study to determine how pretest counseling impacts cancer knowledge, psychosocial development, and decision-making about genetic testing for patients with breast cancer. They analyzed 103 patients, 87 of whom had undergone surgery and 16 of whom had not. The patients ranged in age from 24 years to 69 years. They met with master's degree-level, trained genetic health professionals to obtain a risk assessment based on their personal and family genetic history. At the same time, they received information about hereditary breast and ovarian cancer as well as the limitations of genetic testing. The study found that both the before-surgery and aftersurgery groups experienced increases in cancer knowledge after pretest genetic counseling. At the same time, the before-surgery group reported decreases in cancer-related distress and intrusive thoughts. Furthermore, informed decision-making in the after-surgery group improved. Dr. Vadaparampil stresses that before-surgery genetic counselors may need to focus on perceived risks of genetic testing and how they might align with patients' values. Reference

Genetic Testing in the Contemporary Diagnosis of Cardiomyopathy

The heritable cardiomyopathies are relatively common conditions that can lead to heart failure and sudden cardiac death. Family history collection, genetic testing and genetic counseling are recommended for these patients and families in multiple practice guidelines and consensus statements. Research discoveries and rapidly dropping costs of DNA sequencing technologies have resulted in the availability of multiple cardiomyopathy genetic testing panels. Genetic testing not only helps in determining the underlying etiology of idiopathic and familial cardiomyopathies, but is also a powerful tool in the determination of which relatives are at-risk and which are not. Both pre- and post-test genetic counseling is an imperative component of genetic testing, as there are many benefits and limitations of genetic testing that need discussed with each patient undergoing this process.

Talking to Parents About Genetics

Talking to Parents About Genetics

Hereditary Hearing Loss: Genetic Counselling

The aim of this review is to provide an updated overview of hereditary hearing loss, with special attention to the etiological diagnosis of sensorineural hearing loss, the genes most frequently mutated in our environment, the techniques available for their analysis and the clinical implications of genetic diagnosis.More than 60% of childhood sensorineural hearing loss is genetic. In adults, the percentage of hereditary hearing loss is unknown. Genetic testing is the highest yielding test for evaluating patients with sensorineural hearing loss. The process of genetic counselling is intended to inform patients and their families of the medical, psychological, and familial implications of genetic diseases, as well as the risks, benefits and limitations of genetic testing. The implementation of any genetic analysis must be always preceded by an appropriate genetic counselling process.

Prioritization of future genetics education for general practitioners: a Delphi study

PurposeGeneral practitioners (GPs) are increasingly expected to deliver genetics services in daily patient care. Education in primary care genetics is considered suboptimal and in urgent need of revision and innovation. The aim of this study was to prioritize topics for genetics education for general practice. MethodsA Delphi consensus procedure consisting of three rounds was conducted. A purposively selected heterogeneous panel (n = 18) of experts, comprising six practicing GPs who were also engaged in research, five GP trainers, four clinical genetics professionals, and three representatives of patient organizations, participated. Educational needs regarding genetics in general practice in terms of knowledge, skills, and attitudes were rated and ranked in a top-10 list. ResultsThe entire panel completed all three rounds. Kendall's coefficient of concordance indicated significant agreement regarding the top 10 genetic education needs (P < 0.001). “Recognizing signals that are potentially indicative of a hereditary component of a disease” was rated highest, followed by “Evaluating indications for referral to a clinical genetics centre” and “Knowledge of the possibilities and limitations of genetic tests.” ConclusionsThe priorities resulting from this study can inform the development of educational modules, including input for case-based education, to improve GP performance in genetic patient care.

Hipoacusias hereditarias: asesoramiento genético

The aim of this review is to provide an updated overview of hereditary hearing loss, with special attention to the etiological diagnosis of sensorineural hearing loss, the genes most frequently mutated in our environment, the techniques available for their analysis and the clinical implications of genetic diagnosis.More than 60% of childhood sensorineural hearing loss is genetic. In adults, the percentage of hereditary hearing loss is unknown. Genetic testing is the highest yielding test for evaluating patients with sensorineural hearing loss. The process of genetic counselling is intended to inform patients and their families of the medical, psychological and familial implications of genetic diseases, as well as the risks, benefits and limitations of genetic testing. The implementation of any genetic analysis must be always preceded by an appropriate genetic counselling process.

Findings from a community education needs assessment to facilitate the integration of genomic medicine into primary care

PurposeTo assess the lay public's knowledge of, and beliefs about, genetics and genetic testing to create an educational initiative that promotes acceptance and utilization of genomic medicine in primary health care. MethodsA telephone survey of English-speaking adults in Guilford County, North Carolina was conducted in 2006 to identify community members' educational needs regarding genetics and genetic testing. ResultsMost respondents recognized the connection between family history and disease risk. A majority did not appear to know about: (1) basic principles of inheritance, (2) laws prohibiting genetic discrimination, and (3) the availability and limitations of genetic tests. About 25% thought that they could not reduce their risk if they have a genetic predisposition for disease. Knowledge level was affected by education, experience, age, and race. ConclusionIf primary care providers use family history as a risk assessment tool, community education programs must address (1) the collection of family health history, (2) legislation regarding genetic nondiscrimination, (3) benefits and limitations of existing genetic tests, and (4) genetic determinism. Programs emphasizing practical, “how to” information can be targeted to individuals likely to collect family history information and address misperceptions about discrimination, testing, and determinism.

Sickle Cell Trait and Sickle Cell Disease: A Case Study

OPEN ACCESSSeptember 22, 2009Sickle Cell Trait and Sickle Cell Disease: A Case Study Shoumita Dasgupta, PhD Shoumita Dasgupta, PhD Boston University School of Medicine Google Scholar More articles by this author https://doi.org/10.15766/mep_2374-8265.7920 SectionsAbout ToolsDownload Citations ShareFacebookTwitterEmail AbstractThis case presents a classic example of an African American individual who is heterozygous for sickle cell disease and who does not manifest any symptoms until he encounters extreme physical conditions. The case explores the initial presentation of sickle cell symptoms in a heterozygote, the assembly of a pedigree and calculation of genetic risk for transmission of the mutation, and the biochemical and genetic testing options that are available for diagnostic and preconception genetic testing in sickle cell disease. This case also covers the strategies governing newborn screening for hemoglobinopathies and their limitations; the genetic concept of compound heterozygosity as it relates to sickle cell and thalassemia mutations in the globin; and the ethical, legal, and societal ramifications of available types of testing strategies. Student evaluations were collected to examine reactions to the case material. In response to the question “What feature(s) most influenced your level of interest in the sickle cell disease case materials?”, a majority of students selected “Motivation to learn concepts of clinical importance.” General student comments included the following: “The questions posed were complex and this definitely encouraged discussion and debate more so than I have seen in other courses,” “I have a much better understanding of the material after sitting with my group and discussing the issues,” and “I would have liked more discussions as I feel I learn better in this format. I'm not a memorizer, so the more interactive a concept is administered to us, the better it is for me. I personally would rather learn lesser details but learn greater conceptual understanding of the material.” Educational Objectives By the end of this case, participants will be able to: Determine which genetic testing methods are most informative and most efficient in different clinical scenarios.Compare and contrast the use of molecular genetic and biochemical testing in establishing the diagnosis of sickle cell disease.Assess the power and limitations of genetic testing as well as the necessity of testing family members' DNA under certain circumstances.Discuss the influence of compound heterozygosity on clinical outcome and management decisions.Describe the social and ethical issues associated with a new diagnosis of sickle cell disease.Explain issues of carrier testing for hemoglobinopathies as they relate to ethnic minority groups and minors. Sign up for the latest publications from MedEdPORTAL Add your email below FILES INCLUDEDReferencesRelatedDetails FILES INCLUDED Included in this publication: SCD Case.pdf To view all publication components, extract (i.e., unzip) them from the downloaded .zip file. Download editor’s noteThis publication may contain technology or a display format that is no longer in use. CitationDasgupta S. Sickle Cell Trait and Sickle Cell Disease: A Case Study. MedEdPORTAL. 2009;5:7920. https://doi.org/10.15766/mep_2374-8265.7920 Copyright & Permissions© 2009 Dasgupta. This is an open-access publication distributed under the terms of the Creative Commons Attribution-NonCommercial-Share Alike license.KeywordsCarrierBlood Coagulation DisordersSickle Cell DiseaseBeta-ThalassemiaHemoglobin SC DiseaseAnemiaSickle Cell TraitMinority HealthHeterozygotePedigree Disclosures None to report. Funding/Support None to report. Prior Presentations Acton RD. Using simulation in medical student education: Teaching Medical Students Surgical and Bedside Skills. Invited panel presentation at the Association for Surgical Education / Association for Program Directors in Surgery annual Surgical Education Week; April 28, 2009; Salt Lake City, UT. Schmitz CC, Acton RD, Gilkeson J, Groth SS, Reihsen T, Neis KS, Chipman JG. Synthesis vs. imitation: Evaluating medical student simulation curriculum via objective structured assessment of technical skills. Poster presented at: Annual meeting of the Association of Surgical Education; April 28–30, 2009; Salt Lake City, UT. Loading ...

The withdrawal from oncogenetic counselling and testing for hereditary and familial breast and ovarian cancer. A descriptive study of an Italian sample

BackgroundOncogenetic counselling is seldom followed through, even when individuals are eligible according to the test criteria. The basic variables which influence the decision to undergo the genetic counselling process are: risk perception, expected benefit or limitations of genetic testing, general psychological distress or cancer-specific distress, lack of trust in one's emotional reactions when faced with negative events, expected level of family support and communications within the family. The aim of this study was to describe the psychosocial variables of an Italian sample that forgoes genetic counselling.MethodsFrom May 2002 to December 2006 a psychological questionnaire was sent out to one hundred and six subjects, who freely requested a first genetic informative consultation, and never asked to have a second visit and the family tree drawn up in order to inquire about their eligibility for genetic testing. Statistical analysis was performed by Pearson chi-square test, t-test and Spearman RHO coefficient.ResultsThe survey presents a lack of emotional cohesion and structured roles and rules within the family system and a positive correlation between the number of children, anxiety and risk perception. The main reasons for giving up on counselling were a sense that testing was a waste of time and the inability to emotionally handle the negative consequences of the test outcome. The subjects who maintained that test and an early diagnosis were a "waste of time" experienced more anxiety.ConclusionThe study revealed the importance to ac knowledging the whole persona and their family system as well as provide information highlighting usefulness of early diagnosis.

Genetic testing for BRCA1: effects of a randomised study of knowledge provision on interest in testing and long term test uptake; implications for the NICE guidelines

Interest in searching for mutations in BRCA1 and BRCA2 is high. Knowledge regarding these genes and the advantages and limitations of genetic testing is limited. It is unknown whether increasing knowledge about breast cancer genetic testing alters interest in testing. Three hundred and seventy nine women (260 with a family history of breast cancer; 119 with breast cancer) from The Royal Marsden NHS Foundation Trust were randomised to receive or not receive written educational information on cancer genetics. A questionnaire was completed assessing interest in BRCA1 testing and knowledge on breast cancer genetics and screening. Actual uptake of BRCA1 testing is reported with a six year follow-up. Eighty nine percent of women at risk of breast cancer and 76% of women with breast cancer were interested in BRCA1 testing (P < 0.0001). Provision of educational information did not affect level of interest. Knowledge about breast cancer susceptibility genes was poor. According to the NICE guidelines regarding eligibility for BRCA1 and BRCA2 testing, the families of 66% of the at risk group and 13% of the women with breast cancer would be eligible for testing (probability of BRCA1 mutation >or=20%). Within six years of randomisation, genetic testing was actually undertaken on 12 women, only 10 of whom would now be eligible, on the NICE guidelines. There is strong interest in BRCA1 testing. Despite considerable ignorance of factors affecting the inheritance of breast cancer, education neither reduced nor increased interest to undergo testing. The NICE guidelines successfully triage those with a high breast cancer risk to be managed in cancer genetics clinics.

Genetic Testing in Parkinson Disease

Parkinson disease (PD) is the second most common neurodegenerative disease. The recent discoveries of a number of disease-causing genes (such as α-synuclein, parkin, UCHL1, PINK1, DJ-1, LRRK2) in PD have generated considerable interest and debate for both physicians and patients regarding diagnostic and presymptomatic genetic testing of PD in the clinic. Of particular significance are reports of a common G2019S mutation of the LRRK2 gene as a cause of familial and sporadic PD across different populations worldwide. This is the first time a common gene mutation has been reported in such an extensive manner across races. However, the feasibility of diagnostic and predictive testing of PD is still beset with many unanswered questions. We discuss the promises and limitations of genetic testing in PD and suggest that many more scientific studies are required before any meaningful guidelines and recommendations for genetic testing in PD can be formulated and broadly implemented.

False‐negative factor V Leiden genetic testing in a patient with recurrent deep venous thrombosis

False-negative genetic testing of the factor V Leiden (fVL) mutation is unusual. We report a case of a young woman with a history of deep venous thrombosis tested for the fVL at four separate laboratories on four separate dates. Two laboratories reported the patient to be heterozygous for the fVL, while the other two reported no evidence of a mutation. Testing methods of the various laboratories were reviewed, and additional testing was performed on stored and newly drawn DNA samples, including sequencing of the fVL gene segment. The preponderance of evidence indicates the patient to be heterozygous for the fVL mutation. Dissection of data suggests that either sample misidentification or faulty allele specific amplification methods could have led to false-negative results in two laboratories. In one of the two laboratories, misinterpretation of results and clerical error could not be excluded. There is a need for standardization of optimized fVL genetic testing methods. Further education of ordering physicians on the limitations of genetic testing is necessary.