Genetic Testing

The introduction of highly active antiretroviral therapy (also known as combination therapy) has transformed the nature of HIV infection from a severe and ultimately fatal disease to that of a manageable chronic condition. HIV drugs are highly efficacious, but their use comes at ...

Among the many educational materials produced by the European Society of Human Reproduction and Embryology (ESHRE) are guidelines. ESHRE guidelines may be developed for many reasons but their intent is always to promote best quality practices in reproductive medicine. In an ...

Lifestyle factors (eg, smoking, diet) and compliance with screening recommendations play a role in cancer risk, and emerging technologies (eg, new vaccines, genetic testing) hold promise for improved risk management. However, optimal outcomes from cancer control efforts require better preparation of health professionals in risk assessment, risk communication, and implementing health behavioral change strategies that are vitally important to cancer control. Although physician assistants (PAs) are substantively engaged in cancer-related service delivery in primary care settings, few models exist to facilitate integration of cancer control learning experiences into the curricula used in intense, fast-paced, 24- to 30-month PA training programs.

Objectives –  During the last years, the association between apolipoprotein E (APOE) polymorphism and disease severity in multiple sclerosis (MS) has been studied with conflicting results. As a result of a considerable individual variation in the clinical course of MS, there is no consensus method for measuring progression using single assessments of disability. Recently, Multiple Sclerosis Severity Score (MSSS) method has been proposed for comparing disease progression using single data. We evaluate in our population if there is any correlation between APOE genotype and severity according to MSSS.Methods –  We studied 82 patients followed up in our Neurology Unit throughout the year 2005, diagnosed with MS, and with disease duration of at least 2 years. We collected data concerning demographic and clinical variables including age of onset, disease duration, Expanded Disability Status Scale (EDSS) score and the total number of relapses. When reached, we determined the latency to EDSS scores of 4.0 and 6.0. We calculated progression index (PI) and relapse rate (RR). We ascertained MSSS for our patients in the global MSSS table.Results –  We found four patients heterozygous for the E2 allele and 16 for the E4 allele. No patient was homozygous for E2 or E4. RR (P = 0.017 with 95% CI: 0.005–0.57) and PI (P = 0.016 with 95% CI: 0.004–0.38) were significantly lower in E4 carriers. MSSS scores were not associated with carriership of E2 or E4.Conclusion –  Our results show no effect of the APOE genotype on the severity of MS measured by MSSS, as a recently published meta-analysis has noticed. So, our data do not support a role for APOE in MS severity, in spite of the seeming influence shown using other measures such as PI. MSSS is probably the best method to measure severity with a single measure of disability and should be used more frequently when performing genetic research.

Isoniazid (INH) is an effective first-line antituberculosis drug. KatG, a catalase-peroxidase, converts INH to an active form in Mycobacterium tuberculosis, and katG mutations are major causes of INH resistance. In the present study, we sequenced katG of 108 INH-resistant M. tuberculosis clinical isolates. Consequently, 9 novel KatG mutants with a single-amino-acid substitution were found. All of these mutants had significantly lower INH oxidase activities than the wild type, and each mutant showed various levels of activity. Isolates having mutations with relatively low activities showed high-level INH resistance. On the basis of our results and known mutations associated with INH resistance, we developed a new hybridization-based line probe assay for rapid detection of INH-resistant M. tuberculosis isolates.

Hypertrophic cardiomyopathy (HCM) is the most prevalent inherited heart disease. Next-generation sequencing (NGS) is the preferred genetic test, but the diagnostic value of screening for minor and candidate genes, and the role of copy number variants (CNVs) deserves further evaluation. Three hundred and eighty-seven consecutive unrelated patients with HCM were screened for genetic variants in the 5 most frequent genes (MYBPC3, MYH7, TNNT2, TNNI3 and TPM1) using Sanger sequencing (N = 84) or NGS (N = 303). In the NGS cohort we analyzed 20 additional minor or candidate genes, and applied a proprietary bioinformatics algorithm for detecting CNVs. Additionally, the rate and classification of TTN variants in HCM were compared with 427 patients without structural heart disease. The percentage of patients with pathogenic/likely pathogenic (P/LP) variants in the main genes was 33.3%, without significant differences between the Sanger sequencing and NGS cohorts. The screening for 20 addition...

Hereditary mixed polyposis is a genetically heterogeneous, autosomal dominant condition with adenomatous, hyperplastic and juvenile polyps. We conducted a comprehensive clinical evaluation of a large Ashkenazi Jewish family with this phenotype and performed extensive genetic testing. As seen in one previous report, a 40 kb duplication upstream of GREM1 segregated with the polyposis/colon cancer phenotype in this kindred. Our study confirms the association of GREM1 with mixed polyposis and further defines the phenotype seen with this mutation. This gene should be included in the test panel for all Jewish patients with mixed polyposis and may be considered in any Ashkenazi patient with unexplained hereditary colon cancer when mutations in other hereditary colon cancer genes have been ruled out.

The introduction of new sequencing technologies whole-genome sequencing (WGS) and whole-exome sequencing (WES) that are much less finely targeted than previous genetic tests has resulted in ethical debate about what should be done with clinically significant findings that may arise during the sequencing process. In this piece we argue that, in addition to whether the finding has been intentionally sought or arises incidentally, the ethical issues concerning what should be done with WES and WGS findings are also influenced by whether sequencing occurs in a clinical or research setting. We argue that decisions about the disclosure of WGS and WES findings generated in the clinical context are much less ethically contentious than decision making about the feedback of research results. We conclude by calling for greater transparency about the purpose of sample collection, more explicit protocols for transitioning between research and clinical contexts and patients and research participan...

Over the past years, one of the most discussed topics in policy debates on genetics has been the use of genetic testing in insurance. Many of these debates have been rather speculative and abstract. In a recent contribution to this journal, Kaufert therefore urged for "a proper research agenda" to study the issue, arguing for the need of anthropological and sociological research of the insurance world. This article will make a start with this. Based on ethnographic fieldwork in two Belgium insurance companies, this study analyses the ways insurers account for predictive medicine (lifestyle, genetics) during underwriting. We demonstrate how insurers highlight predictive lifestyle health information and how this articulates with a fault based approach in underwriting. Individual responsibility for health risks becomes the golden standard for assessing one's fitness for membership of the insurance pool. Moreover, these developments imply a changed concept of "normal standard" in insurance, increasing the conditions to fulfil to be part of the insurance group. Predictive medicine constitutes new ground in the old debates about individual control, responsibility and blame for health. This goes to the heart of the basis for citizenship and how this articulates with membership--or, if you want, exclusion--of the insurance pool.

It is studied the psychosocial impact of Counselling Genetic Oncology (CGO) on the participants who have received the genetic test results. A sample of 59 participants that had undertaken genetic testing and received results was assessed by The Multidimensional Impact of Cancer Risk Assessment (MICRA) Questionnaire.It was studied possible differences in psychosocial impact according to: result type of, previous oncologist diagnosis, time passed from result communication and type of hereditarysyndrome. The outcomes showed that GCO does notproduce negative psychosocial impact. There were not differences by previous diagnosis,time communication and type of hereditary syndrome on MICRA. It is necessary more research for Spanish MICRA adaptation with the purpose to dispose of a specific instrument effective for psyhosocial impact study of genetic testing.

Individuals at increased risk of developing breast cancer due to their family history of the disease face a number of uncertainties. Personal cancer risk estimates are imprecise and current methods for early detection or prevention are not 100% effective. It is therefore not surprising that adverse psychosocial outcomes have been described within this population. Research attempting to predict the incidence of distress and dysfunction in individuals at increased risk of cancer has been largely a-theoretical and has overlooked a number of potentially important predictive variables. In particular, the influence of personal experience of cancer through involvement with affected relatives has been neglected. There are strong theoretical grounds for hypothesising that dimensions of personal experience may influence response to cancer risk. This paper discusses the potential impact of personal experience on risk perception, illness representations and decision-making. Systematic research ...

Catholic movements within the centre of Roman Catholic doctrine recently have discussed Trinitarian theology as applied to sciences, arts, economics, health and other social areas. We explore the possibilities Trinitarian theology offers to bioethical debate, concentrating particularly on genetic screening and testing. It is important therefore to analyse the philosophical implications of this approach onto the bioethical world, where much disagreement occurs on fundamental issues. It is Catholic basic teaching to recognize and see God's hand in plurality, not merely as a cliche and then doing what we feel is right, but to recognize how to live in a pluralistic world. We recognize, in agreement with these theologians, that in order for a Trinitarian mode of understanding to be used by those doing bioethical debate, there is a need to depart from fundamentalism.