College Of Medical Research Articles

Cystic fibrosis testing 8 years on: Lessons learned from carrier screening and sequencing analysis

PurposeThis study reviews data from our cystic fibrosis testing program to evaluate the performance of population-based carrier screening and compare observed detection rates with predicted results of the American College of Medical Genetics/American College of Obstetricians and Gynecologists recommended panel of 23 mutations. MethodsWe queried our proprietary databases containing approximately 3 million cystic fibrosis screening tests, 1300 prenatal diagnostic tests, and 2400 cystic fibrosis sequencing analyses. ResultsWe observed an overall cystic fibrosis carrier frequency of 1:37.6 individuals in the pan-ethnic tested population. This represents a detection rate of 77%, given an estimated US pan-ethnic carrier frequency of 1:29. For patients self-identified as white or Ashkenazi Jewish, a carrier frequency of 1:29 and 1:27 were observed, respectively. A combined frequency of 1:28, representing close to 90% of carriers, was identified in these two highest risk populations. In total, 119 affected fetuses were identified by prenatal diagnoses, a ratio of 1 affected fetus per 25,000 carrier screens. Of 62 newborns with positive immunoreactive trypsinogen and positive sweat tests, almost all of whom had been tested using the American College of Medical Genetics/American College of Obstetricians and Gynecologists panel, only two individuals would have been identified using an expanded mutation panel. ConclusionThe American College of Medical Genetics/American College of Obstetricians and Gynecologists panel of 23 mutations is performing as predicted in detecting cystic fibrosis carriers in the United States among all ethnic groups. No recurrent mutations have been detected in sufficient numbers to justify including any additional mutations to the existing panel. An expanded American College of Medical Genetics/American College of Obstetricians and Gynecologists panel would have a minimal impact on the prevention of births of children affected with cystic fibrosis. Genet Med 2011:13(2):166–172.

Wiring Economy of Neocortical Axon Arbors

Event Abstract Back to Event Wiring Economy of Neocortical Axon Arbors J. M. Budd1*, K. Kovács2, A. S. Ferecskó3, P. Buzás4, U. T. Eysel2 and Z. F. Kisvárday5 1 University of Sussex, School of Informatics, United Kingdom 2 Ruhr-Universität Bochum, Department of Neurophysiology, Germany 3 University of Birmingham, College of Medical & Dental Sciences, School of Clinical & Experimental Medicine, United Kingdom 4 University of Pécs, Institute of Physiology, Medical School, Hungary 5 University of Debrecen, Department of Anatomy, Histology & Embryology, Hungary Discovering the organizational principles of cerebral cortex represents a fundamental challenge in neuroscience. Rámon y Cajal proposed that general laws of conservation concerning cellular material (axon and dendritic ‘wire’) and conduction delay regulate neuronal morphology. Yet despite more than a century of research it is not known how well these laws apply to axon arbors in neocortex. Using a variety of graph optimization algorithms, we investigated Cajal’s proposed economy laws in relation to detailed 3D reconstructions of spiny and basket cell axon arbors obtained from in vivo labelling experiments in adult cat visual cortex. Our analysis of these data suggests that individual neocortical axon arbors are not minimized for axonal length (cellular material) but neither are they optimized for conduction delay. Instead neocortical axon arbors in contacting thousands of spatially distributed postsynaptic targets appear to trade-off saving axonal wire for more rapid communication. In particular, the branched structure of neocortical arbors seems to preserve the relationship between axonal propagation latency and cortical distance and ensures a low degree of temporal dispersion axonal latencies, which may be tighter for inhibitory basket cell than excitatory spiny cell axons. This work has implications for our understanding of neocortical organizing principles, coding, and communication. Acknowledgements Research funded by MTA-TKI (242), DFG (SFB509), and the FACETS (FP6-IST-FETPI) project. Keywords: Molecular and cellular neurobiology, Neuroscience Conference: 13th Conference of the Hungarian Neuroscience Society (MITT), Budapest, Hungary, 20 Jan - 22 Jan, 2011. Presentation Type: Abstract Topic: Molecular and cellular neurobiology Citation: Budd JM, Kovács K, Ferecskó AS, Buzás P, Eysel UT and Kisvárday ZF (2011). Wiring Economy of Neocortical Axon Arbors. Front. Neurosci. Conference Abstract: 13th Conference of the Hungarian Neuroscience Society (MITT). doi: 10.3389/conf.fnins.2011.84.00101 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 03 Mar 2011; Published Online: 23 Mar 2011. * Correspondence: Dr. J. M Budd, University of Sussex, School of Informatics, Brighton, United Kingdom, kisvarday@anat.med.unideb.hu Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers J. M Budd K. Kovács A. S Ferecskó P. Buzás U. T Eysel Z. F Kisvárday Google J. M Budd K. Kovács A. S Ferecskó P. Buzás U. T Eysel Z. F Kisvárday Google Scholar J. M Budd K. Kovács A. S Ferecskó P. Buzás U. T Eysel Z. F Kisvárday PubMed J. M Budd K. Kovács A. S Ferecskó P. Buzás U. T Eysel Z. F Kisvárday Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Why an aspirin a day no longer keeps the doctor away …

Aspirin, which has just celebrated its 111th anniversary, remains one of the most widely used antiplatelet agents worldwide (1). Its high efficacy has made aspirin the cornerstone of treatment in patients suffering from cardiovascular diseases; indeed, daily aspirin therapy reduces the risk of stroke, myocardial infarction and death by approximately 25% (2). Early investigation into aspirin’s pharmacology revealed an asymmetry between its pharmacokinetics and pharmacodynamics (3). Despite aspirin’s short half-life in blood of approximately 30 minutes, once daily aspirin administration in doses as low as 40 mg per day has been shown to induce cumulative, profound and sustained inhibition of platelet function (4). Moreover, there is no clear evidence to suggest that doses higher than 100 mg daily increase aspirin’s antithrombotic efficacy, whereas the bleeding risk associated with taking aspirin appears to be dose-dependent (2). For this reason, a fixed regimen of once daily low-dose aspirin has been adopted into all relevant treatment guidelines. While it is true in most cases that an aspirin a day keeps the doctor away, it would also appear that not all patients benefit from the drug to the same extent as others (5). In this issue of Thrombosis and Haemostasis, Henry et al. have explored whether once daily low-dose aspirin provides sustained inhibition of platelet function throughout the 24-hour dosing interval in 150 stable coronary artery disease (CAD) patients (6). The major finding of the study is that in up to 25% of patients, platelets recover their ability to aggregate within 24 hours of the last aspirin dose, thus potentially leaving patients unprotected against thrombotic events at the end of the dosing interval (6). The study leaves the reader with a number of unanswered questions: (a) what are the underlying mechanisms leading to this uncharacteristically fast recovery of platelet function in some CAD patients taking aspirin daily; and (b) what can be done about it? To answer the first question, one must first consider whether this phenomenon is substantiated. In this regard, it is interesting to note that this is not the first report of significant recovery of platelet function within 24 hours of aspirin administration. Perneby et al. have shown in healthy volunteers that platelets can recover their ability to aggregate within 24 hours of various doses of aspirin ranging from 37.5 mg to 960 mg (7). Recovery of platelet function was also shown in stable CAD patients in a small series of 11 patients on daily aspirin therapy (8). Thus, the study by Henry et al. confirms and extends these findings to a larger CAD population. Taken together, these studies suggest that while aspirin is effective in inhibiting platelet aggregation within one hour of administration (thus eliminating the most common causes of a lack of platelet inhibition by aspirin, such as non compliance, reduced aspirin bioavailability, and drug interactions), this inhibition is not sustained for the whole dosing interval in certain individuals. This of course begs the question why. Aspirin inhibits platelet aggregation by irreversibly acetylating a key enzyme in the conversion of arachidonic acid into thromboxane (Tx) A2, namely cyclooxygenase (COX)-1 (9). As a result, TxA2 formation and consequent platelet aggregation is almost completely abolished throughout the platelet lifespan of 7–10 days, and platelet function is regained by Correspondence to: Dr. Marie Lordkipanidze Centre for Cardiovascular Sciences Institute of Biomedical Research College of Medical and Dental Sciences University of Birmingham Edgbaston, Birmingham B15 2TT, UK Tel: +44 121 415 8680, Fax: +44 121 415 8817 E-mail: m.lordkipanidze@bham.ac.uk

Locus heterogeneity and Knobloch syndrome

Locus Heterogeneity and Knobloch Syndrome Sarah Joyce, Louise Tee, Aiysha Abid, Shagufta Khaliq, S. Qasim Mehdi, and Eamonn R. Maher* Department of Medical and Molecular Genetics, School of Clinical and Experimental Medicine, Institute of Biomedical Research, University of Birmingham College of Medical and Dental Sciences, Birmingham, UK Centre for Human Genetics, Sindh Institute of Urology & Transplantation, Karachi, Pakistan Regional Genetics Service, Birmingham Women’s Hospital, Birmingham, UK

The Differential Profiles of Withdrawal Symptoms and Regulation of Signal Molecules and Gene Expressions Induced by i.c.v. Morphine and Beta-Endorphin

Event Abstract Back to Event The Differential Profiles of Withdrawal Symptoms and Regulation of Signal Molecules and Gene Expressions Induced by i.c.v. Morphine and Beta-Endorphin Soo-Hyun Paks1*, Yun-Beom Sim1, Seung-Min Choi1, Jin-Koo Lee1 and Hong-Won Suh1 1 Institute of Natural Medicine, College of Medicine, Hallym University, Medical and Bio-Materials Research Center and Department of Pharmacology, South Korea In this study, withdrawal symptoms induced by morphine (MOR) and beta-endorphin (BEND) administered i.c.v. were compared in ICR mice. In addition, the differential regulation of signal transduction molecules and several gene expressions were assessed in the various brain regions. To perform, naloxone (NAL) was post-treated i.p. 3 hours after either a single or repeated (1 time/day for 3 days) injection with MOR or BEND. Withdrawal symptoms were observed for 30 min immediately after NAL treatment. The jumping, diarrhea, weight loss, rearing, penile licking and paw tremor observed in NAL/MOR treated group was persistently increased during 3 days. On the other hand, the diarrhea, weight loss and rearing induced by NAL/BEND treatment were increased after single injection with BEND, but gradually decreased after repeated injection with BEND. Furthermore, no jumping, penile licking and paw tremor in NAL/BEND treated group were observed throughout whole period of time. In molecular assay, various brain regions were dissected each at 30min, 1 hour and 2 hours after NAL treatment. The POMC, CRH and c-Fos gene expressions may be involved both the supraspinal MOR or BEND treatment and withdrawal in various brain regions. In addition, acute or chronic MOR or BEND treatment and withdrawal were regulated by nearly similar signal transduction molecules mechanisms, but chronic BEND withdrawal could not modulate the pCaMK-II activity in the various brain regions. These results suggest that withdrawal symptoms profiles of MOR or BEND administered supraspinally appear to be differentially regulated. Furthermore, the acute and chronic MOR or BEND treatment and withdrawal were regulated by nearly similar signal transduction molecules mechanisms and gene expressions. On the other hand, supraspinally repeated treatment-induced chronic withdrawal state of MOR or BEND was differential regulated the Ca2+-dependent signal-regulated molecules such as pCaMK-II in the various brain regions. Conference: IBRO International Workshop 2010, Pécs, Hungary, 21 Jan - 23 Jan, 2010. Presentation Type: Poster Presentation Topic: Cognition and behavior Citation: Paks S, Sim Y, Choi S, Lee J and Suh H (2010). The Differential Profiles of Withdrawal Symptoms and Regulation of Signal Molecules and Gene Expressions Induced by i.c.v. Morphine and Beta-Endorphin. Front. Neurosci. Conference Abstract: IBRO International Workshop 2010. doi: 10.3389/conf.fnins.2010.10.00178 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 30 Apr 2010; Published Online: 30 Apr 2010. * Correspondence: Soo-Hyun Paks, Institute of Natural Medicine, College of Medicine, Hallym University, Medical and Bio-Materials Research Center and Department of Pharmacology, Chuncheon, South Korea, shyun1017@hanmail.net Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Soo-Hyun Paks Yun-Beom Sim Seung-Min Choi Jin-Koo Lee Hong-Won Suh Google Soo-Hyun Paks Yun-Beom Sim Seung-Min Choi Jin-Koo Lee Hong-Won Suh Google Scholar Soo-Hyun Paks Yun-Beom Sim Seung-Min Choi Jin-Koo Lee Hong-Won Suh PubMed Soo-Hyun Paks Yun-Beom Sim Seung-Min Choi Jin-Koo Lee Hong-Won Suh Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Probing Different Time-Scales of Oscillatory Fluctuations in Visual Awareness: From Behavior to Phase

1 Centre for Cognitive Neuroimaging, Institute of Neuroscience and Psychology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK 2 Wellcome Trust Centre for Neuroimaging at University College London, Institute of Neurology, University College London, London, UK 3 Institute of Cognitive Neuroscience, University College London, London, UK *Correspondence: nienke@psy.gla.ac.uk

18 Impact of dietary augmentation with dried whole fruit, vegetable and berry juice concentrates upon outcomes of periodontal therapy: a randomized controlled trial

M.M. Milward1, N. Ling-Mountford1, P. Weston1, G.E. Dallal2, J.B. Matthews1, S. De-Spirt3, W. Stahl3, I.L.C. Chapple1. 1Periodontal Research Group, College of Medical and Dental Sciences, The University of Birmingham, UK; 2Biostatistics Unit, USDA HNRC at Tufts University, Boston, MA, USA; 3Institut fuer Biochemie und Molekularbiologie I Heinrich-Heine-Universitaet, Duesseldorf, Germany E-mail: m.r.milward@bham.ac.uk Chronic periodontitis is the most prevalent chronic inflammatory disease of humans [1], a major cause of tooth loss [2] and an independent risk factor for systemic inflammatory diseases, such as atherogenic vascular disease [3], type-2 diabetes [4] and rheumatoid arthritis [5]. It is caused by a dysregulated inflammatory response to the microbial plaque biofilm, characterised by oxidative stress [6], and which fails to remove causative pathogens, creating a non-resolving inflammation that destroys the attachment of the teeth to jaw bone. Large epidemiological studies have demonstrated an inverse association between serum antioxidant micronutrient levels and periodontitis prevalence [7]. Therefore, the aim of this placebo-controlled, randomized, double blind trial, was to assess whether additional benefit could be obtained by use of dietary augmentation with dried whole fruit, vegetable and berry extracts (Juice Plus+®), employed during and after non-surgical periodontal therapy. Primary outcome measures were reductions in periodontal pocket depth (PPD) and gain in connective tissue attachment level (CAL) to teeth, 2-months following standard therapy. Test interventions were fruit/vegetable (FV, n = 16) and FV/berry (FVB, n = 15) verses placebo (PL, n = 17). Statistical analysis employed 2-tailed ANCOVA (baseline PPD and CAL as covariates) and interim data on 48 never smokers are reported. Plasma beta-carotene concentrations increased over the study period in FV and FVV groups (p 0.05), and were higher at 2-months in FV and FVV than PL (p < 0.006). Non-surgical therapy produced statistically significant improvements in PPD (FV = 0.86±0.4mm; FVB = 0.88±0.4mm; PL = 0.81±0.5mm) and for CAL (p < 0.0001). Despite such large improvements, additional benefit was seen for PPD with FV (p < 0.03) and FVB (p < 0.04) supplementation versus PL, and a trend towards additional gains in CAL with FV (p = 0.07). Thus, adjunctive antioxidant micronutrients (Juice Plus+®) may offer additional therapeutic benefit to standard non-surgical periodontal therapy. Support: NSA (TN, USA).

What is the role of radioiodine uptake measurement and thyroid scintigraphy in the diagnosis and management of hyperthyroidism?

Clinical EndocrinologyVolume 72, Issue 1 p. 11-12 What is the role of radioiodine uptake measurement and thyroid scintigraphy in the diagnosis and management of hyperthyroidism? Jayne A. Franklyn, Jayne A. Franklyn School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UKSearch for more papers by this author Jayne A. Franklyn, Jayne A. Franklyn School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UKSearch for more papers by this author First published: 14 December 2009 https://doi.org/10.1111/j.1365-2265.2009.03633.xCitations: 13 Professor J. A. Franklyn, 2nd Floor Institute of Biomedical Research, The Medical School, University of Birmingham, Birmingham B15 2TT, UK. Tel: +44 121 4143711; Fax: +44 121 4158712; E-mail: j.a.franklyn@bham.ac.uk Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume72, Issue1January 2010Pages 11-12 RelatedInformation

Hexaketides from Phytopathogenic Fungus Paraphaeosphaeria recurvifoliae

College of Medical and Life Sciences, Silla University, Busan 617-736, Korea. *E-mail: hoh@silla.ac.kr Department of Applied Bioscience and Biotechnology, Environmental-Friendly Agriculture Research Center, College of Agriculture and Life Sciences, Chonnam National University, Gwangju 500-757, Korea Department of Biotechnology and Bioengineering, Pukyong National University, Busan 608-237, Korea Department of Microbiology and Immunology, Pusan National University School of Medicine, Busan 602-739, Korea *E-mail: ahnsc@pusan.ac.kr Received July 16, 2007

Defining purpose: a key step in genetic test evaluation

The introduction of new genetic tests, like other medical innovations, can be conceptualized as a three-step process. Tests are proposed for use based on research findings and clinical reasoning; an evaluation occurs; and judgments are made about clinical use and reimbursement (Fig. 1). The evaluation may be informal, as when a clinician determines whether a new test will be helpful in a particular patient encounter, or formal, as when a practice guideline panel utilizes a defined methodology to assess a test or a health care funder utilizes a set of criteria to determine test coverage. Although genetic tests are often described in terms of technology, a full evaluation requires that the test be considered as a clinical process in which the laboratory assay, or other testing procedure, is done to acquire information about a particular health condition, in a defined population, for a specific clinical purpose.1 Genetic tests have a wide range of health care applications. They are used to confirm the presence of a genetic condition, identify reproductive risks, and select preventive therapy. Testing occurs in newborn screening programs and in primary, specialty, and prenatal care, and may be initiated on the basis of clinical symptoms, family history, or population demographics. Genetic tests also utilize a range of technologies, and vary considerably in their predictive value. This diversity poses a challenge for the evaluation process. Several groups have considered methods for genetic test evaluation,2–5 and model programs for systematic evaluation have been established in the United States (Evaluation of Genomic Applications in Practice and Prevention6) and the UK (the UK Genetic Testing Network7). To date, however, the evaluation process has not fully addressed the clinical diversity of genetic tests. The Evaluation of Genomic Applications in Practice and Prevention project has focused on genetic tests related to common disorders and drug therapy, whereas the United Kingdom Genetic Testing Network has primarily addressed tests for single gene disorders. An effort by the Secretary’s Advisory Committee on Genetic Testing to categorize genetic tests into those requiring higher versus lower levels of scrutiny was not successful.8 To address the challenge of genetic test diversity, we propose an outcome-orientated taxonomy for defining test purpose. A focus on health outcomes allows the definition of a small and informative set of purposes for genetic testing, despite the range of technologies and clinical settings in which testing occurs. Defining test purpose in turn clarifies the benefits to be expected from the testing process, and provides guidance to clinicians and policy makers concerning the evidence needed to support test use. Defining test purpose, therefore, is an important first step in genetic test evaluation.

Longitudinal Evaluation of "Presymptomatic" Carriers of Huntington's Disease

Longitudinal Evaluation of "Presymptomatic" Carriers of Huntington's Disease

A Comparative Study of Five Technologically Diverse CFTR Testing Platforms

Multiple cystic fibrosis (CF) testing platforms, using diverse and rapidly evolving technologies, are available to clinical laboratories commercially or for evaluation. Considerations when choosing a CF platform may include: sensitivity, specificity, accuracy, signal discrimination, ability to genotype, ability to reflex test, no calls/repeat rate, composition of mutation panel, hands-on time, start-to-finish time, integration into laboratory workflow, data analysis methods, flexibility regarding custom test design, and required instrumentation. Mindful of these considerations, we evaluated five technologically diverse CF platforms: 1) eSensor, an electronic detection assay system; 2) InPlex, a signal amplification methodology using a microfluidics card; 3) oligonucleotide ligation assay, an electrophoretic-based separation of amplicon-derived ligation-generated products; and two liquid bead arrays; 4) Signature, a direct hybridization assay using allele-specific capture probes; and 5) Tag-It, an assay using allele-specific primer extension and a universal microarray. A core of 150 samples, focusing on mutations in the American College of Medical Genetics/American College of Obstetricians and Gynecologists mutation panel, was tested throughout several runs for each platform. All of the platforms performed comparably in respect to sensitivity, specificity, and no-call rate. As our results indicate, consideration of all of the parameters evaluated may be useful when selecting the most appropriate platform for the specific setting.

Evidence for HIV-2 infection in Nepal

Assessment of the presence and prevalence of HIV-2 antibodies in patients attending the Universal Collegeof Medical Sciences Teaching Hospital, Bhairahawa, western Nepal was done. A total of 1534 patients serawere screened for the presence of HIV-1 and HIV-2 antibodies from March 2000 to May 2003. A total of 3(0.195%) patients were found to be sero-positive for HIV-2 antibodies. Out of the above three patients, 1(0.065%) was infected with HIV-2 only and the remaining 2 (0.13%) were infected with HIV-1 and HIV -2 both. This evidence of HIV-2 presence implicates serious outcomes as HIV-2 has not been reported fromhospital patients in Nepal.Key Words: HIV-2, sero-prevalence, hospital patients, AIDS.

Estimated analytic validity of HFE C282Y mutation testing in population screening: The potential value of confirmatory testing

Purpose The purpose of this study was to estimate analytic sensitivity and specificity of HFE testing for C282Y homozygosity in the hypothetical setting of population screening for hemochromatosis.Methods We analyzed published results of the Molecular Genetics Survey performed by the American College of Medical Genetics/College of American Pathologists between 1998 and 2002, taking into account its educational nature.Results Analytic sensitivity for C282Y homozygosity is 98.4% (95% CI 95.9%–99.5%). The analytic specificity is 99.8% (99.4%–99.9%). At a frequency of 40 per 10,000 for the homozygous genotype, the analytic positive predictive value is 66%.Conclusion HFE testing for C282Y homozygosity is highly reliable. Homozygosity is uncommon in population screening, however, and confirmatory testing should be considered.

Tandem mass spectrometry in newborn screening: American College of Medical Genetics/American Society of Human Genetics Test and Technology Transfer Committee Working Group

Tandem mass spectrometry in newborn screening: American College of Medical Genetics/American Society of Human Genetics Test and Technology Transfer Committee Working Group

Statement on use of apolipoprotein E testing for Alzheimer disease. American College of Medical Genetics/American Society of Human Genetics Working Group on ApoE and Alzheimer disease

To evaluate the published data on the association between apolipoprotein E genotype (APOE) and Alzheimer disease (AD) and determine whether the data support the use of genetic testing for diagnosis or prediction of disease. This statement is intended for neurologists, psychiatrists, geneticists, primary care providers, diagnostic laboratories, and the public.The joint American College of Medical Genetics (ACMG) and American Society of Human Genetics (ASHG) Test and Technology Transfer Committee developed a 10-member ACMG/ASHG Working Group to assess available data on the association of AD with APOE alleles. To ensure inclusion of clinical specialists primarily involved with AD patients and families, the American Academy of Neurology (AAN) and the American Psychiatric Association (APA) appointed liaisons to the Working Group.Peer-reviewed journal publications obtained from an Index Medicus search or known to members of the Working Group were the source of data on which the statement is based.Following discussions with all members of the Working Group, a draft statement was prepared by the chair and circulated among all members until a consensus was reached. The consensus draft was sequentially reviewed and endorsed by the appropriate scientific and executive committees of the ACMG, ASHG, AAN, APA, and the National Institutes of Health-Department of Education Working Group on Ethical, Legal, and Social Implications of Human Genome Research. In some instances, suggestions from these committees were incorporated into the final statement.There is general consensus that APOE epsilon 4 is strongly associated with AD and that when present may represent an important risk factor for the disease. However, at the present time it is not recommended for use in routine clinical diagnosis nor should it be used for predictive testing. Studies to date indicate that the APOE genotype alone does not provide sufficient sensitivity or specificity to allow genotyping to be used as a diagnostic test. Because AD develops in the absence of APOE epsilon 4 and because many with APOE epsilon 4 seem to escape disease, genotyping is also not recommended for use as a predictive genetic test. The results of a collaborative study under way will clarify some of these issues. Whether APOE genotypes have other uses in the management of AD will become apparent over the next few years.