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Genetic research gained new momentum with the completion of the Human Genome Project in 2003. Formerly centered on the investigation of single-gene disorders, genetic research is increasingly targeting common complex diseases and in doing so is studying the whole genome, the environment and its impact on genomic variation. Consequently, biobanking initiatives have emerged around the world as a tool to sustain such progress. Whether they are small scale or longitudinal, public or private, commercial or non-commercial, biobanks should consider the possibility of closure. Interestingly, while raising important ethical issues, this topic has hardly been explored in the literature. Indeed, ethical issues associated with sale, insolvency, end of funding, or transfer of materials to other entities (which are all issues either related to or possible consequences of closure) are seldom the subject of discussion. In an attempt to fill this gap, this paper will discuss-using population and direct-to-consumer (DTC) genetic testing companies' biobanks as case studies-(1) international and national normative documents addressing the issue of closure and (2) the internal policies of population biobanks and DTC genetic testing companies. The analysis will inform the debate on biobank closure and elucidate the underlying ethical issues, which include, but are not limited to informed consent, storage and privacy.

Objective: To determine the impact which introduction of the 11-14 week scan has had on the gestational age at which fetal malformations are detected by ultrasound in an unselected population of pregnant women., Design: Retrospective study., Setting: University hospital, Copenhagen, Denmark, covering the period 1 January 2003 to 30 June 2007., Population: All pregnant women who chose a nuchal translucency scan at 11-14 weeks for Down syndrome risk estimate, and a scan at 18-20 weeks to screen for fetal malformations., Methods: Review of cases detected ante- and postnatally., Main Outcome Measures: Detection rates at 11-14 weeks relative to all malformations in the population., Results: A total of 216 anomalies were detected in 200 fetuses among the 9 324 fetuses included, while 70 anomalies were diagnosed in 59 infants postnatally. The prevalence of fetuses with anomalies was 2.8% (259 of 9 324). After excluding cases of pyelectasis (127), which may be considered physiological and transitory changes, the prevalence of malformed fetuses was 1.4% (132 of 9 324). Of the malformations detected antenatally, 25.8% were detected before week 15 and 59.6% in weeks 16-22. The remaining 14.6% of malformations were discovered after week 22. Among the lethal malformations, 50% were diagnosed before week 15., Conclusions: Although the purpose of the first trimester scan is to screen for Down syndrome and not for malformations, the introduction of the 11-14 week scan has resulted in the detection of approximately 26% of fetal malformations., (© 2011 The Authors Acta Obstetricia et Gynecologica Scandinavica© 2011 Nordic Federation of Societies of Obstetrics and Gynecology.)

Objective: Newborn hearing screening has been widely adopted and made an achievement to some degree. Current screening protocols rely solely on detecting existing auditory disorders at the time of screening and are unable to identify individuals susceptible to auditory disorders in later life. Even if the hearing loss newborn is referred, most cases could not be diagnosed until 6-12 months old with no etiology being elucidated. This study reports the first effort to combine traditional hearing screening with genetic screening to improve the efficacy of newborn hearing screening., Methods: This study was undertaken in 12 regional hospitals located in 11 provinces of China. 14,913 newborn babies received hearing concurrent genetic screening. The hearing screening was performed with OAE or AABR. Blood sample was collected with a universal newborn genetic screening card. And three common gene, mtDNA 12S rRNA, GJB2 and SLC26A4 were screened with standard protocol., Results: Among all the 14,913 newborns, 86.1% (12,837/14,913) individuals passed the first-step hearing screening, 7.8% (1168/14,913) babies passed only one side, and the other 6.1% (908/14,913) were bilaterally referred. Gene screening found 306 individuals had one or two mutant alleles, the carrier rate is 2.05% (306/14,913) among the entire newborn population. The risk for hearing loss was 100% (7/7) for those newborns carrying causative GJB2 or SLC26A4 mutations (homozygotes or compound heterozygotes), 14.4% (23/160) for GJB2 heterozygote carriers, 12.3% (15/122) for SLC26A2 heterozygous carriers, and the total prevalence of referral hearing screening was approximately 14.7% (45/306). However, 85.3% (261/306) newborns passed hearing screening among these carriers including 18 newborns with 12S rRNA mt.1555A>G pathogenic mutation, who would suffer from sudden hearing loss once applying aminoglycoside drugs., Conclusion: The cohort studies provided the essential population parameters for developing effective programs for hearing care of newborns in China. Hearing concurrent gene screening in newborns may confirm the abnormal results from hearing screening tests, help to find the etiologic of the hearing loss, and better recognize infants at risk for late-onset hearing loss occurring prior to speech and language development. In conclusion, a survey on 14,913 Chinese newborns proved that concurrent genetic screening could improve newborn hearing screening for hearing defects., (Crown Copyright © 2011. Published by Elsevier Ireland Ltd. All rights reserved.)

Objectives: To describe critical elements of cancer risk assessment as identified through professional standards., Data Sources: Professional guidelines, policy statements, and other published literature., Conclusion: The continually increasing integration of genetics/genomics into oncology care mandates that oncology nurses be familiar with the cancer risk assessment process, complexities, and implications for personalized risk reduction and early detection recommendations and for cancer treatment, including targeted therapies., Implications for Nursing Practice: Informed nurses can identify genetic cancer risk factors, educate patients about cancer risk and risk management/treatment strategies, and refer appropriate patients to a cancer genetics nurse or other genetics professional for comprehensive risk assessment., (Copyright © 2011 Elsevier Inc. All rights reserved.)

With the ever-widening gap between what is technologically possible and services available, jurisdictions around the world are faced with complex decisions regarding the introduction and expansion of genetic screening programs. A series of literature reviews and consultations with stakeholders and experts led to the development of a decision support guide for genetic screening policy-making. This involved establishing a preliminary list of core criteria synthesized from the growing literature on genetic screening, which was then transformed through a series of consultations into a more elaborate decision guide. Although certain perennial challenges in genetic screening policy-making remain, the decision support guide aims to promote a fair and evidence-informed process that makes explicit the ethical dilemmas often inherent to such policy decisions., (Copyright © 2009 S. Karger AG, Basel.)

Background: Multiple endocrine neoplasia type 1 (MEN1) is associated with significant morbidity and mortality. Timely detection of MEN1 kindred, together with treatment of associated tumours, results in an improved outcome. We describe how the development of a dedicated multidisciplinary MEN clinic has improved the diagnosis and treatment of MEN1-associated endocrinopathies., Design and Patients: A dedicated MEN clinic was developed at Aintree University Hospital, Liverpool in 2002 for patients living in Merseyside, Cheshire and North Wales. The multidisciplinary approach adopted, aimed to improve communication and continuity of care. Patients see all clinicians involved in their care (Consultant Endocrinologist, Paediatrician, Clinical Geneticist and Endocrine Surgeon) simultaneously, allowing for a unified, clear approach and a reduction in unnecessary attendances. The clinicians adopt a proactive approach to tracing the relatives of patients, with the aim of identifying kindred with previously asymptomatic disease., Results: In 2002, 16 patients from 5 families were diagnosed clinically with MEN1. Twenty MEN1-associated endocrinopathies had been diagnosed and 21 surgical procedures had been performed. By the end of 2008, 45 patients from 15 families had been identified, with 83 endocrinopathies diagnosed and 50 surgical procedures performed. Ninety-four known relatives are awaiting screening for MEN1., Conclusion: The successful identification of patients with MEN1 has resulted in an exponential increase in the number of patients attending the clinic. As relatives undergo screening, the diagnosis of MEN is likely to increase. The ever increasing numbers of patients requiring screening, surveillance and treatment has implications in the planning of future service provision.

There is accumulating evidence that women with breast cancer due to a familial BRCA1 or BRCA2 mutation benefit from specific surgical and chemotherapeutic treatment strategies. However, the rapid identification of such patients during the acute phase of treatment raises a number of issues. This study investigated Australian opinion leaders' views on the issues arising from such 'treatment-focused' genetic testing. Semi-structured interviews with 34 opinion leaders working in cancer genetics were undertaken. Interviewees acknowledged the introduction of treatment-focused DNA testing has the potential to positively transform the management of breast cancer patients, but were concerned that certain ethical and logistical issues have yet to be addressed. These include decision-making and consent, the familial nature of genetic information, and the management of genetics services within familial cancer clinics in the public hospital system in Australia. Service providers will need to have policies and strategies for managing the increased demand. It will also be necessary to include genetic counseling services within familial cancer clinics in the care pathway for newly diagnosed patients prior to any DNA testing to determine adjuvant treatment; such services may be more cost-effective than expecting surgeons and medical oncologists to fulfill this role.

Objective: Policy-makers are faced with increasing pressures from a range of different stakeholders to introduce or expand genetic screening programmes. A shared understanding is therefore needed of the many factors influencing these complex policy decisions. Our aim was to develop a theoretical framework that highlights the multiple components and influences involved in genetic screening and the policy-making process., Methods: As part of a larger research programme, existing policy frameworks relating to genetic screening were identified through a review of the literature. Major themes were identified and synthesized into an overarching framework, which was further refined through discussions with key informants., Results: The framework consists of three parts. The first part conceptualizes genetic screening as an integrated public health programme. The second part describes the policy-making process at each stage in the life cycle of the programme. The third part depicts the broader context within which policy-making occurs., Conclusion: This framework can support policy-makers by fostering a common understanding and facilitating dialogue with stakeholders. The framework has also been used as the conceptual foundation for the development of a more elaborate decision-guide.

Objectives: To assess the effectiveness, cost-effectiveness, acceptability and feasibility of offering universal antenatal sickle cell and thalassaemia (SCT) screening in primary care when pregnancy is first confirmed and to model the cost-effectiveness of early screening in primary care versus standard care., Design: A population-based cohort study, cluster randomised trial and refinement of a published decision model., Setting: Twenty-five general practices from two UK primary care trusts (PCTs) in two inner city boroughs with a high proportion of residents from minority ethnic groups., Participants: Practices were considered eligible if they agreed to be randomised and they were able to provide anonymous data on all eligible pregnant women. Participants were at least 18 years old and consented to take part in the evaluation., Interventions: Practices were allocated to intervention, using minimisation and stratifying for PCT and number of partners at the practice, as follows: screening in primary care with parallel father testing (test offered to mother and father simultaneously; n = 8 clusters, 1010 participants); screening in primary care with sequential father testing (test offered to father only if mother identified as carrier; n = 9 clusters, 792 participants); and screening in secondary care with sequential father testing (standard care; n = 8 clusters, 619 participants)., Main Outcome Measures: Data on gestational age at pregnancy confirmation and screening date were collected from trial practices for 6 months before randomisation in the cohort phase. The primary outcome measure was timing of SCT screening, measured as the proportion of women screened before 70 days' (10 weeks') gestation. Other outcomes included: offer of screening, rates of informed choice and proportion of women who knew the carrier status of their baby's father by 77 days (11 weeks)., Results: For 1441 eligible women in the cohort phase, the median [interquartile range (IQR)] gestational age at pregnancy confirmation was 7.6 weeks (6.0 to 10.7 weeks) and 74% presented in primary care before 10 weeks. The median gestational age at screening was 15.3 weeks (IQR 12.6 to 18.0 weeks). Only 4.4% were screened before 10 weeks. The median delay between pregnancy confirmation and screening was 6.9 weeks (4.7 to 9.3 weeks). In the intervention phase, 1708 pregnancies from 25 practices were assessed for the primary outcome measure. Completed questionnaires were obtained from 464 women who met eligibility criteria for the main analysis. The proportion of women screened by 10 weeks (70 days) was 9/441 (2%) in standard care, compared with 161/677 (24%) in primary care with parallel testing, and 167/590 (28%) in primary care with sequential testing. The proportion of women offered screening by 10 weeks (70 days) was 3/90 (3%) in standard care (note offer of test ascertained for questionnaire respondents only), compared with 321/677 (47%) in primary care with parallel testing, and 281/590 (48%) in primary care with sequential testing. The proportion of women screened by 26 weeks (182 days) was similar across the three groups: 324/441 (73%) in standard care, 571/677 (84%, 0.09) in primary care with parallel testing, and 481/590 (82%, 0.148) in primary care with sequential testing. The screening uptake of fathers was 51/677 (8%) in primary care with parallel testing, and 16/590 (3%) in primary care with sequential testing, and 13/441 (3%) in standard care. The predicted average total cost per pregnancy of offering antenatal SCT screening was estimated to be 13 pounds in standard care, 18.50 pounds in primary care with parallel testing, and 16.40 pounds in primary care with sequential testing. The incremental cost-effectiveness ratio (ICER) was 23 pounds in primary care with parallel testing and 12 pounds in primary care with sequential testing when compared with standard care. Women offered testing in primary care were as likely to make an informed choice as those offered screening by midwives later in pregnancy, but less than one-third of women overall made an informed choice about screening., Conclusions: Offering antenatal SCT screening as part of pregnancy-confirmation consultations significantly increased the proportion of women screened before 10 weeks (70 days), from 2% in standard care to between 16% and 27% in primary care, but additional resources may be required to implement this. There was no evidence to support offering fathers screening at the same time as women., Trial Registration: Current Controlled Trials ISRCTN00677850.

The Israeli population is characterized by unique demographic features including high genetic homogeneity within many closed communities. As a consequence the molecular epidemiology of epidermolysis bullosa differs markedly in this country and surrounding areas from that reported in the Western world., (Copyright 2010 Elsevier Inc. All rights reserved.)

Objective: The aim of this study was to collect the practices of cytogenetic and molecular genetic testing and genetic counseling activities in Italy in the year 2007 and provide guidance to the national and regional health systems to improve the organization of genetic services., Methods: A web-based survey was carried out to assess the total number and the type of analyses, the number and type of genetic counseling sessions, and the personnel attending these activities. The quality management system of the responding structures, in terms of certification and accreditation standards, was also investigated. The appropriateness of requests for genetic testing was evaluated for six disorders., Results: Data were collected from 278 responding centers, half of which were located in the northern regions of the country. Twenty-eight percent of the total were certified according to quality standards. A total of 217 molecular genetic and 171 cytogenetic laboratories, and 102 clinical genetic services were surveyed. About 560,000 genetic tests, including 311,069 cytogenetic and 248,691 molecular genetic analyses of 556 genes, were recorded. The fetal karyotype was examined on either trophoblast or amniocytes in about one of every 4.4 pregnancies. Only 11.5% of cytogenetic analyses and 13.5% of molecular tests were accompanied by genetic counseling. Concerning the appropriateness of a request for genetic testing, a low congruity was found between the clinical diagnosis and the laboratory results., Conclusion: This study highlights the need for reorganizing the genetic structure network in Italy, which at present is oversized, improving the quality management systems, expanding the availability of testing for rare disease genes, and improving access to pretest and posttest genetic counseling.

Introduction: Due to the lack of precise diagnostic criteria, current search strategy for monogenic diabetes is predominantly based on atypical clinical course of diabetes and intuition of the attending physician. Yet another issue is the common view that monogenic diabetes is rare. It discourages from performing deepened diagnostics and makes it difficult to gain experience necessary to select appropriate patients for genetic examination., Aim of the Study: Estimating the true incidence of patients with a high probability of monogenic background of the disease and compare their search strategies based on clinical practice or structured databases., Material and Methods: The authors compared the current strategy of selecting candidates for screening with a directed search strategy based on immunologic (lack of islet autoantibodies), functional (presence or complete lack of c-peptide at onset and follow-up) and familial (dominant pattern of inheritance) criteria. The number of patients selected for the screening was chosen as efficacy measure selected among 1281 diabetic patients diagnosed and treated between 1983-2009., Results: Screening based on clinical assessment yielded 37 patients (2.9%) chosen for genetic screening. Criteria used by the physicians were based on up-to-date guidelines and unusual clinical course. Active search of the database according to predefined criteria resulted in selecting: 121 patients (9.4%) with likely monogenic background of diabetes (71 - lack of autoantibodies, 8 - normal C-peptide, 6 - lack of both c-peptide and autoantibodies, 36 - diabetes in at least one parent). The difference in screening efficacy was statistically significant (p <0.0001)., Conclusions: Periodic reevaluation of patients' data allows a significant increase in the number of candidates subjected to genetic screening and potentially achieving beneficial therapeutic effects by means of pharmacogenetics.

The Human Genome Project will change how health is defined and how disease is prevented, diagnosed, and treated. As the largest group of health care providers in contact with patients, nurses need to be competent in the science of genetics. Beyond this, nurses need to understand the complexities that arise in genomic health care. Ethical, legal, and social issues are integral to the delivery of genomic health care, and nurses must have an astute understanding of such complexities. What it means to know, to reason, and to act in this postgenomic age is explored.

Objective: To assess whether knowledge of insurance implications influenced uptake of genetic testing by participants in a research study of the causes of colorectal cancer., Design, Setting and Participants: Analysis of uptake of genetic testing by participants in the population-based Victorian Colorectal Cancer Family Study during two periods: from 1999 to 2003, when participants were not informed of any potential effect of genetic testing conducted during the study on their eligibility for new insurance policies; and from 2003 to 2006, when the protocol was changed to provide participants with information on the potential effect of genetic testing on insurance eligibility., Main Outcome Measure: Uptake of genetic testing for germline mutations in DNA mismatch repair (MMR) genes at a family cancer clinic., Results: The proportion of participants who declined genetic testing among those informed of insurance implications was more than double the proportion among those without this knowledge (29/59 [49%] v 9/47 [19%]; P = 0.002). This difference could not be explained statistically by adjusting for measured putative predictors., Conclusion: Identification of people with a mutation in an MMR gene has clinical importance, and such screening may be a cost-effective way to reduce the burden of colorectal cancer in the community. If people are choosing not to obtain genetic information because of how it will affect their eligibility for insurance, reforms to existing insurance practices are indicated.

Third party payers, funding agencies, and lawmakers often require clinicians and public health agencies to justify programs and services by documenting results. This article describes two assessment tools--"Defining Genetics Services Framework" and "Genetics Services Outcomes Menu," created to assist public health professionals, clinicians, family advocates, and researchers to plan, evaluate, and demonstrate the effectiveness of genetics services. The tools were developed by a work group of the Western States Genetics Services Collaborative (WSGSC) consisting of public health genetics and newborn screening professionals, family representatives, a medical geneticist, and genetic counselors from Alaska, California, Hawaii, Idaho, Oregon, and Washington. The work group created both tools by an iterative process of combining their ideas with findings from a literature and World Wide Web review. The Defining Genetics Services Framework reflects the diversity of work group members. Three over-lapping areas of genetics services from public health core functions to population screening to clinical genetics services are depicted. The Genetics Services Outcomes Menu lists sample long-term outcomes of genetics services. Menu outcomes are classified under impact areas of Knowledge and Information; Financing; Screening and Identification; Diagnosis, Treatment, and Management; and Population Health. The WSGSC incorporated aspects of both tools into their Regional Genetics Plan., (2009 Wiley-Liss, Inc.)

The Professional Practice and Guidelines Committee of the American College of Medical Genetics has the responsibility of overseeing the development of guidelines for the practice of clinical genetics. In the past, most, if not all, guidelines were primarily based on expert opinion. However, recently the goal has become to develop guidelines that are more evidence-based, or at least, to recognize the level of evidence available to the authors of these documents. This article reviews the challenges that are faced by geneticists who are charged with the development of practice guidelines., (2009 Wiley-Liss, Inc.)

As genetic services grow in scope, issues of quality assessment in genetic services are emerging. These efforts are well developed for molecular and cytogenetic testing and laboratories, and newborn screening programs, but assessing quality in clinical services has lagged, perhaps owing to the small work force and the recent evolution from a few large training programs to multiple training sites. We surveyed the English language, peer-reviewed literature to summarize the knowledge-base of quality assessment of genetics services, organized into the tripartite categories of the Donabedian model of "structure," "process," and "outcome." MEDLINE searches from 1990 to July 2008, yielded 2,143 articles that addressed both "medical/genetic screening and counseling" and "quality indicators, control, and assurance." Of the 2,143 titles, 131 articles were extracted for in-depth analysis, and 55 were included in this review. Twenty-nine articles focused on structure, 19 on process, and seven on outcomes. Our review underscored the urgent need for a coherent model that will provide health care organizations with tools to assess, report, monitor, and improve quality. The structure, process, and outcomes domains that make up the quality framework provide a comprehensive lens through which to examine quality in medical genetics., (2009 Wiley-Liss, Inc.)

Population genetic screening programs for carrier detection of severe genetic disorders exist worldwide, mainly for beta-thalassemia. These screening programs are either mandatory or voluntary. In several Arab countries and Iran, the state has made thalassemia carrier detection mandatory, while tests for detecting carriers are required by the religious authorities in Cyprus. In all the existing mandatory genetic screening programs, the couples have to get the information about the tests before marriage, but the decision whether or not to marry is left to them. Voluntary programs exist for instance in several Mediterranean countries for the prevention of thalassemia and for several genetic diseases among Jews. While voluntary programs leave the decision to be screened or not to the individual, a major problem is that in many cases awareness about the existence of screening tests is very sparse. Some programs, for instance in Canada or Australia, therefore provide education about genetic tests and screening at school in order to allow the individuals to be able to make an informed decision about their reproductive choices.

In recent years, preimplantation genetic diagnosis (PGD) has developed into a routine diagnostic procedure in health care. Although during this process, several initiatives have been employed to regulate the procedure, access to PGD may be hampered by the diversity in health-care arrangements or therapeutic cultures in different countries. This article demonstrates how PGD provision practices depend on much more than regulation alone, by providing an in-depth comparative analysis of the provision of PGD in Britain, the Netherlands and Germany. In analysing regulation, organization, selection of indications, and mechanisms and criteria for reimbursement, differences between these countries can be identified. This is important, since differences in PGD provision can have enormous consequences for the access of individual patients in different countries. Somewhat paradoxically, this article concludes that even though differences in access do have serious consequences, they also serve the establishment of PGD. Developing access to PGD in national 'therapeutic cultures' can contribute to making PGD routine health care in a way that may not be achievable by harmonizing regulation.

Hereditary breast and ovarian cancer syndrome is an inherited cancer-susceptibility syndrome. The hallmarks of this syndrome are multiple family members with breast cancer or ovarian cancer or both, the presence of both breast cancer and ovarian cancer in a single individual, and early age of breast cancer onset. Clinical genetic testing for gene mutations allows physicians to more precisely identify women who are at substantial risk of breast cancer and ovarian cancer. For these individuals, screening and prevention strategies can be instituted to reduce their risks. Obstetricians and gynecologists play an important role in the identification and management of women with hereditary breast and ovarian cancer syndrome.

The neonate born with a genetic defect or fetal anomaly presents a challenge to the neonatal intensive care unit team. Typically genetic disorders are thought of as being rare; however, this is not true, and it is becoming increasingly evident as knowledge and technology progress. A definitive diagnosis is essential for management and care of the neonate and the neonate's family. An evidence-based approach to the neonate who has a suspected genetic anomaly is essential to provide accurate diagnosis and to guide ongoing care. This article gives an overview of basic genetics and genetic counseling, and applies the principles to two case studies.

The goal of the Human Genome Diversity Project (HGDP) was to reconstruct the history of human evolution and the historical and geographical distribution of populations with the help of scientific research. Through this kind of research, the entire spectrum of genetic diversity to be found in the human species was to be explored with the hope of generating a better understanding of the history of humankind. An important part of this genome diversity research consists in taking blood and tissue samples from indigenous populations. For various reasons, it has not been possible to execute this project in the planned scope and form to date. Nevertheless, genomic diversity research addresses complex issues which prove to be highly relevant from the perspective of research ethics, transcultural medical ethics, and cultural philosophy. In the article at hand, we discuss these ethical issues as illustrated by the HGDP. This investigation focuses on the confrontation of culturally diverse images of humans and their cosmologies within the framework of genome diversity research and the ethical questions it raises. We argue that in addition to complex questions pertaining to research ethics such as informed consent and autonomy of probands, genome diversity research also has a cultural-philosophical, meta-ethical, and phenomenological dimension which must be taken into account in ethical discourses. Acknowledging this fact, we attempt to show the limits of current guidelines used in international genome diversity studies, following this up by a formulation of theses designed to facilitate an appropriate inquiry and ethical evaluation of intercultural dimensions of genome research.

Prevention of sickle cell anemia, a severe and painful disease, relies on carrier detection and information, and on prenatal diagnosis with the possibility of medical abortion. Here we report the first results of a medical and welfare program launched in Paris 20 months ago and dedicated to sickle cell carrier screening and information.

Initial guidelines for cystic fibrosis (CF) carrier screening were issued in 2001 by the American College of Medical Genetics and the American College of Obstetricians and Gynecologists and updated in 2004. It is unknown how these guidelines have influenced laboratory practice. This study examined the uptake of two components of these guidelines for CF screening in genetic testing laboratories. A survey of directors of US genetic testing laboratories was conducted. Of 190 respondents, 178 answered questions about CF testing. Nearly half (49%) performed some type of DNA testing for CF; most of these (92%) performed CF carrier screening. Ten percent used a 23-mutation panel for CF screening. The results of 5T tests were reported as a reflex test by 79% of laboratories, while 8% always returned 5T results and 7% never returned them. Seven percent of laboratories adopted both guidelines, 80% adopted one of the two guidelines, and 13% had not adopted either recommendation, suggesting that factors other than clinical guidelines may influence laboratories' CF screening practices. Further studies are needed to determine whether the adoption of CF screening guidelines has significant clinical or economic effects on population-based CF screening programs.

Objectives: To describe optimization of a nationwide newborn screening program for cystic fibrosis (CF) that combines an immunoreactive trypsinogen (IRT) assay and DNA mutation analysis in dried blood samples at day 3., Study Design: Data from regional screening laboratories and CF care centers were centralized and periodically analyzed to allow adaptation, thus limiting the number of false-positive cases., Results: A total of 2717905 infants were screened between 2002 and 2005. Flow chart protocol was modified twice. First, the IRT d3 cutoff value increased from 60 to 65 microg/L, thus decreasing the percentage of samples requiring mutation analysis from 0.82% to 0.64%. Second, for infants with no mutations using the screening panel, a recall for IRT was performed only if IRT d3 was > 100 microg/L; the percentage of recalls decreased from 0.51% to 0.12%, and the percentage of infants requiring a sweat test decreased from 0.14% to 0.01%. No significant change in the CF detection rate was observed after these 2 modifications. A total of 625 CF cases were detected, and 22 false-negative findings (3.4%) were observed, most of them inevitable, with a low initial IRT., Conclusions: The centralized data analysis led to changes in the screening strategy to optimise the newborn screening program.

In the last ten years there has been a rapid expansion in the number of genetic tests and increased interest in accessing the information available through these tests. The expansion of access to genetic testing occurs against the background of mixed systems for delivering health services, including DNA testing. This paper draws on theory relating to the social shaping of technologies and the concept of technological 'scripts' to offer a critical analysis of recent debate in Aotearoa New Zealand about private provision of genetic testing. An apparent 'turf war' between professionals about who will provide genetic tests obscures attention to a more serious issue--the redefinition of a technology. What is at stake is not just who will do the tests, but what technology is available--either genetic testing as a commodity, or an integrated set of genetic services. While focused on a particular national context, this paper addresses issues relevant to the provision of genetic services in other nation states characterised by a mixture of public and private provision of health services.

Purpose: To describe and discuss the characteristic features and red flags of Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer, that warrants referral for genetic cancer risk assessment (GCRA). A focus on the nurse practitioner's (NP) role in familial risk assessment, physical examination, initiation of genetic referrals, and issues related to the genetic counseling process are also discussed., Data Sources: A review and synopsis of professional guidelines, clinical articles, and research studies on Lynch syndrome and the genetics of inherited cancer syndromes associated with colorectal cancer. Online resources from the American Gastroenterological Association, American Medical Association, the American Nurses Association, the National Comprehensive Cancer Network, the National Cancer Institute, the National Cancer Institute-Physician Data Query, the National Coalition of Health Professional Education in Genetics, the National Human Genome Research Institute, the National Society of Genetic Counselors, International Society of Nurses in Genetics, and the Oncology Nursing Society., Conclusions: Approximately 5% of all colon cancers are because of a germ line mutation predisposing individuals and their family members to colorectal and other cancers. Although the efficacy of screening modalities is established, healthcare providers often fail to identify those at greatest risk for disease. The extended family history is the first step in recognition of individuals "suspect" for hereditary colon cancers such as Lynch syndrome. Early-age onset of Lynch syndrome-associated cancers, an autosomal-dominant pattern, multiple primary tumors in an individual or multiple family members with Lynch syndrome-associated cancers, characteristic pathological features of colon cancer, or a known germ line Lynch syndrome mutation in a family member are "red flags" that will aid NPs in identifying individuals who may benefit from GCRA. IMPLICATIONS FOR NURSE PRACTITIONER PRACTICE: The importance of enhanced surveillance for early diagnosis and prevention of disease is a critical part of primary care. Thus, it is imperative that NPs obtain a minimum of a three-generation pedigree, recognize hereditary cancer patterns, and provide referral counseling for consideration of genetic testing of individuals suspect for Lynch syndrome.

Background: Hirschsprung's disease (HSCR) represents a complex disorder of signaling molecules, resulting from the effects of at least 9 known susceptibility genes. Affected families carry 200 times higher risk, but genetic counseling via pedigree analysis is difficult and the significance of genetic variations is unclear. This study evaluated a set of patients affected by HSCR with familial recurrence to evaluate factors of greatest value in genetic counseling., Patients and Methods: One hundred twenty patients with HSCR (including 18 kindreds) were screened for genetic variations of the 2 major susceptibility genes (RET and endothelin B receptor [EDNRB]) and compared with 60 control samples (20 per ethnic group). Familial recurrence patterns were studied for patient sex, pattern of recurrence, presence of associated syndromic features, and genetic features of major susceptibility genes. Polymerase chain reaction and HEX-SSCP analysis were performed on DBA extracted from blood/microdissected tissue samples. SSCP variants were validated and automated sequencing techniques performed on polymerase chain reaction products showing conformational variants in acrylamide gel., Results: Familial cases had a male-female ratio of 1.5:1, male-to-male transmission (n = 10; 2 father to son), female-to-male transmissions (n = 4; 3 female carriers, female-to-female (n = 4; 2 mother to daughter), and 1 paternal RET deletion-female with very long segment aganglionosis. Increasing gene penetrance occurred in 3 pedigrees. An increased incidence of long segment HSCR was noted in families with recurrence and appeared important. No consistent mendelian trends or specific genetic sites were observed, but 3 suggested autosomal dominant and recessive in a further 3. Identified genetic variations included deletions, frame shifts, and missense mutations, as well as a number of significant single nucleotide polymorphism variations. Transmitted RET mutations occurred in 5 (30%) of 16 kindreds. Splice RET mutation plus variants of exon 17 (973L) affected 2 children with identical total colonic aganglionosis. In a 3-generation family, variations in RET exons 6, 13, and 18 (928) affected 3 male children with increasing penetration to recur as total intestinal aganglionosis in a grandchild., Conclusions: Mendelian transmission appears mediated by the RET proto-oncogene. EDNRB mutations suggest haplotypic gene-gene interaction. Genetic counseling remains a challenge in HSCR because of its multfactorial etiology.

Recent clinical study reported that the best choosing of antiretroviral therapy for an individual patients is one that physicians have always tried to practice, making use of whatever knowledge or tools are available to treatment decisions. Individual genetic variations provide scope for a wide range of host-drug interactions that will differentiate therapeutic outcomes within an otherwise homogenous population. Pharmacogenetics looks set to become an increasingly important field to refine the medical tools to personalize antiretroviral treatment. The integration of genetic tests into routine patient management has a great challenge for HIV-guidelines and for clinical care. Pharmacogenetics will increasingly impact all medical disciplines for the candidates to therapy. It was confirmed, that genetic screening enabled to prevent abacavir hypersensitivity reaction.

Objectives: In this paper we describe the outline and results of a 7-year screening programme for thalassaemias and glucose-6-phosphate dehydrogenase (G6PD) deficiency in 13- to 14-year-old students from the Sardinian population., Method: This programme had several steps: formal education on thalassaemia, request of informed consent by parents, blood testing and genetic counselling., Results: Out of 63,285 subjects tested, 6,521 (10.3%) were heterozygotes for beta-thalassaemia, 16,175 (25.6%) for alpha-thalassaemia and 101 were carriers of a haemoglobin variant. One thousand four hundred and twenty (16.4%) males were hemizygotes for G6PD deficiency and 1,893 (20.6%) females were heterozygotes., Conclusion: The uptake of the programme was remarkably high and homogeneous across the island, indicating and confirming a great interest of the Sardinian population in any initiative directed at the prevention of homozygous beta-thalassaemia., ((c) 2008 S. Karger AG, Basel)

The UK Department of Health supported the establishment of the UK Genetic Testing Network (UKGTN) in 2002. The UKGTN is a collaborative network of NHS molecular genetic laboratories that offer tests for human single gene germ-line disorders. Its objective is to provide high quality and equitable services for patients and their families who require genetic advice, diagnosis and management. The UKGTN has developed a 'Gene Dossier' process to evaluate genetic tests and recommend which tests will be provided by the National Health Service. This paper describes the UKGTN organisation and the 'Gene Dossier' process. A brief review of the UKGTN genetic test evaluation experience is presented.

Background: Alpha-1-antitrypsin deficiency (AATD) is significantly underdiagnosed. The early detection of AATD would enable affected persons to make lifestyle changes such as quitting smoking. It was the aim of the study to determine whether the combination of an awareness program with the offer of a cost-free diagnostic test results in the identification of a significant number of individuals with severe AATD., Methodology: We combined a series of measures to promote awareness with the offer of a diagnostic test at no charge. Test blood was applied to a filter paper and sent to our laboratory. The level of AAT was measured by nephelometry, the presence of the S- or Z-allele was determined by PCR, and phenotyping was performed by isoelectric focusing., Results: During 37 months 17688 testing kits were distributed and 2722 were sent back to our laboratory. We identified 335 patients with severe AATD including 16 individuals with rare genotypes. Prescreening by determining the AAT serum levels by the submitting physician increased the detection rate as compared to similar programs that screened unselected individuals., Summary: These data show that the combination of an awareness program with the offer of free diagnostic testing results in the identification of a large number individuals with severe AATD.

In 2005, a federal advisory committee recommended that the number of disorders in state newborn screening programs be expanded from 9 to 29. In view of this recommendation, state leaders will need to make cogent decisions regarding the expanse of their state newborn screening programs. They must consider several factors, including the costs and outcomes of the screening program. The expense of the initial screening test can be misleading because it does not include the cost of the entire program (testing, tracking, notifying, retesting, confirmatory testing, and follow-up). Also, outcomes such as false positive findings can be costly to newborn screening programs, result in additional testing for infants, and lead to parental concern and worry. This article examines some of the policy issues related to newborn screening and specifically focuses on three disorders recommended for newborn screening, cystic fibrosis (CF), medium-chain acyl CoA dehydrogenase Deficiency (MCADD), and beta-ketothiolase (BKT).

Approximately 5% to 10% of breast and ovarian cancers are related to an inherited gene mutation. Of these cases, 84% of hereditary breast cancer and more than 90% of hereditary ovarian cancer are caused by mutations in the BRCA1 or BRCA2 genes. Family histories of cancer are an essential tool in identifying features of and individuals at risk for hereditary breast-ovarian cancer syndrome. The risk to carry an identifiable BRCA gene mutation can be assessed by trained healthcare providers using various pre-test risk models. Individuals who carry a BRCA gene mutation have increased lifetime risks of developing hereditary breast and ovarian cancer syndrome-related cancers. Genetic testing for the BRCA gene mutations is offered in accordance with American Society of Clinical Oncology guidelines. In accordance with guidelines, patients are informed of the risks, benefits, and limitations of testing prior to electing to undergo the testing process. Upon receipt of results, healthcare providers offer the patient with appropriate medical management recommendations.