Ethical Issues in Contemporary Clinical Genetics.

As genetic sequencing capabilities become more powerful and costs decline, the reach of genomics is expanding beyond research laboratories to the wards, outpatient clinics, and, with the marketing of direct-to-consumer testing services, patients' homes. Increasingly, patients receiving various diagnoses-from cancer to cardiomyopathy-can reasonably expect to have conversations with their providers about indications for genetic testing. In this dynamic context, a grasp of the ethical principles and history underlying clinical genetics will provide clinicians with the tools to guide their practice and help patients navigate complex medical-psychosocial terrain. This article provides an overview of the salient ethical concerns pertaining to clinical genetics. The subject is approached with an emphasis on clinical practice, but consideration is also given to research. The review is organized around the temporal and informational sequence of issues commonly arising during the course of pretesting, testing, and posttesting phases of patient care. Drawing from medical, legal, and historical perspectives, this review covers the following topics: (1) informed consent, (2) return of results, and (3) privacy and confidentiality, and intends to equip readers with an appropriate foundation to apply ethical principles to genetic testing paradigms with an understanding of the contextual landscape against which these situations occur.

Experience, knowledge, and opinions about childhood genetic testing in Batten disease.

BACKGROUND AND OBJECTIVES: Policies for genetic testing in children (GTIC) focus on medical or psychosocial benefit to the child, discouraging or prohibiting carrier testing, and advising caution regarding pre-symptomatic diagnosis if no treatment exists. This study sought to understand parents' perspectives on these issues and determine their experiences and knowledge related to genetic testing for Batten disease - a set of inherited neurodegenerative diseases of childhood onset for which no disease modifying therapies yet exist. METHODS: Parents of children with Batten disease completed a survey of their knowledge of genetics, experience with genetic testing, and opinions regarding GTIC. RESULTS: 54% had sought genetic testing for non-affected family members, including predictive diagnosis of healthy, at-risk children. Participation in any genetic counseling was associated with greater knowledge on questions about genetics. The majority of parents felt it was better to know ahead of time that a child would develop Batten disease, believed that this knowledge would not alter how they related to their child, and that parents should have the final say in deciding whether to obtain GTIC. CONCLUSIONS: Parents of children with an inherited disease are knowledgeable about genetics and wish to establish predictive or carrier status of at-risk children.

Genetics and genomics of pulmonary arterial hypertension.

Major discoveries have been obtained within the last decade in the field of hereditary predisposition to pulmonary arterial hypertension (PAH). Among them, the identification of bone morphogenetic protein receptor type 2 (BMPR2) as the major predisposing gene and activin A receptor type II-like kinase-1 (ACVRL1, also known as ALK1) as the major gene when PAH is associated with hereditary hemorrhagic telangiectasia. The mutation detection rate for the known genes is approximately 75% in familial PAH, but the mutation shortfall remains unexplained even after careful molecular investigation of these genes. To identify additional genetic variants predisposing to PAH, investigators harnessed the power of next-generation sequencing to successfully identify additional genes that will be described in this report. Furthermore, common genetic predisposing factors for PAH can be identified by genome-wide association studies and are detailed in this paper. The careful study of families and routine genetic diagnosis facilitated natural history studies based on large registries of PAH patients to be set up in different countries. These longitudinal or cross-sectional studies permitted the clinical characterization of PAH in mutation carriers to be accurately described. The availability of molecular genetic diagnosis has opened up a new field for patient care, including genetic counseling for a severe disease, taking into account that the major predisposing gene has a highly variable penetrance between families. Molecular information can be drawn from the genomic study of affected tissues in PAH, in particular, pulmonary vascular tissues and cells, to gain insight into the mechanisms leading to the development of the disease. High-throughput genomic techniques, on the basis of next-generation sequencing, now allow the accurate quantification and analysis of ribonucleic acid, species, including micro-ribonucleic acids, and allow for a genome-wide investigation of epigenetic or regulatory mechanisms, which include deoxyribonucleic acid methylation, histone methylation, and acetylation, or transcription factor binding.

Knowledge of the Genetic Information Nondiscrimination act among individuals affected by Huntington disease.

The Genetic Information Nondiscrimination Act (GINA) of 2008 was the first US legislation to address genetic discrimination. We sought to assess understanding of GINA among individuals affected by the autosomal dominant condition, Huntington disease (HD). We conducted a cross-sectional survey of individuals with varying risk of HD to assess their familiarity with GINA. As a control, individuals were surveyed about their familiarity with the Health Insurance Portability and Accountability Act (HIPAA). Those who reported familiarity with GINA were asked about their knowledge of specific provisions of the legislation. The survey was offered to 776 participants and completed by 410 (response rate 53%). Respondents across all groups were less familiar with GINA (41% slightly, somewhat, or very familiar) than with HIPAA (65%; p < 0.0001). Of individuals with or at risk for HD who reported some familiarity with GINA, less than half correctly identified GINA's protections, and less than 15% correctly identified its limitations. Thus, among individuals affected by HD, familiarity with and knowledge of GINA are low. The effectiveness of the legislation may be limited by this lack of knowledge.