Clinical Genetics in Britain: Origins and development

Annotated and edited transcript of a Witness Seminar held on 23 September 2008. Introduction by Professor Sir John Bell, Uiversity of Oxford.First published by the Wellcome Trust Centre for the History of Medicine at UCL, 2010.©The Trustee of the Wellcome Trust, London, 2010.All volumes are freely available online at: www.history.qmul.ac.uk/research/modbiomed/wellcome_witnesses/Annotated and edited transcript of a Witness Seminar held on 23 September 2008. Introduction by Professor Sir John Bell, Uiversity of Oxford.Annotated and edited transcript of a Witness Seminar held on 23 September 2008. Introduction by Professor Sir John Bell, Uiversity of Oxford.Annotated and edited transcript of a Witness Seminar held on 23 September 2008. Introduction by Professor Sir John Bell, Uiversity of Oxford.Annotated and edited transcript of a Witness Seminar held on 23 September 2008. Introduction by Professor Sir John Bell, Uiversity of Oxford.Annotated and edited transcript of a Witness Seminar held on 23 September 2008. Introduction by Professor Sir John Bell, Uiversity of Oxford.Annotated and edited transcript of a Witness Seminar held on 23 September 2008. Introduction by Professor Sir John Bell, Uiversity of Oxford.Clinical genetics has become a major medical specialty in Britain since its beginnings with Lionel Penrose’s work on mental handicap and phenylketonuria (PKU) and John Fraser Robert’s first genetic clinic in 1946. Subsequent advances in diagnosis and prediction have had key impacts on families with inherited disorders and prospective parents concerned about their unborn children. The Witness Seminar focused on the beginnings of British clinical genetics in London, Oxford, Liverpool and Manchester, the development of subspecialties, such as dysmorphology, and also the roles of the Royal College of Physicians, the Clinical Genetics Society and the Department of Health in the establishment of clinical genetics as a specialty in 1980. Specialist non-medical genetic counsellors, initially from the fields of nursing and social work, progressively became a more significant part of genetic services, while lay societies also developed an important influence on services. Prenatal diagnosis became possible with the introduction of new genetic tools in regional centres to identify fetal anomalies and chromosomal disorders. This volume complements the 2001 Witness Seminar on genetic testing which emphasizes laboratory aspects of medical genetics, with limited coverage of clinical genetics. Participants include: Ms Chris Barnes, Dr Caroline Berry, Professor Martin Bobrow (chair), Professor Sir John Burn, Dr Ian Lister Cheese, Professor Angus Clarke, Dr Clare Davison, Professor Joy Delhanty, Dr Nick Dennis, Professor Dian Donnai, Professor Alan Emery, Professor George Fraser, Mrs Margaret Fraser Roberts, Professor Peter Harper, Dr Hilary Harris, Professor Rodney Harris, Professor Shirley Hodgson, Dr Alan Johnston, Mrs Ann Kershaw, Mrs Lauren Kerzin-Storrar, Professor Michael Laurence, Professor Ursula Mittwoch, Professor Michael Modell, Professor Marcus Pembrey, Professor Sue Povey, Professor Heather Skirton, Professor Sir David Weatherall. Harper P A, Reynolds L A, Tansey E M. (eds) (2010) Clinical genetics in Britain: Origins and development. Wellcome Witnesses to Twentieth Century Medicine, vol. 39. London: The Wellcome Trust Centre for the History of Medicine at UCL.The Wellcome Trust Centre for the History of Medicine at UCL is funded by the Wellcome Trust, which is a registered charity, no. 210183

Potentializing Newborn Screening

Virtually all 4.25 million babies born annually in the United States are screened for more than 50 rare genetic conditions. In a country plagued with widespread health-service access problems, this remarkable public health achievement depends on policy visions of newborn screening as the linchpin of secondary prevention and saving children's lives. Based on ethnographic research and drawing from a semiotic framework, we illustrate that newborn screening has had a much wider range of effects in the clinic than those anticipated by policy makers. How does the disconnect between policy potential and clinical experience affect the technology? We demonstrate that only some discrepancies are considered in policy circles and that instead, parents, geneticists, and policy makers renew visions of potentiality that preserve the technology's benefits in spite of evidence to the contrary. While rearticulating the potential of technologies may help actors cope with situations that do not measure up to expectations, the inevitable cost of reformulating potentiality once a technology has been implemented is that some accumulated experiences will be rendered invisible. © 2013 by The Wenner-GrenFoundation for Anthropological Research. All rights reserved

Tracing the shifting sands of ‘medical genetics’: what’s in a name?

This paper focuses on the structural development of institution-based interest in genetics in Anglo-North American medicine after 1930 concomitantly with an analysis of the changes through which ideas about heredity and the hereditary transmission of diseases in families have passed. It maintains that the unfolding relationship between medicine and genetics can best be understood against the background of the shift in emphasis in conceptualisations of recurring patterns of disease in families from ‘biological relatedness’ to ‘related to chromosomes and genes.’ The paper begins with brief considerations of the historical confluences of, first, heredity and medicine and, second, genetics and medicine which, in a third section, leads to a discussion about a uniquely ‘genetics-based approach’ to medicine in the second half of the twentieth-century

Outlook Magazine, Winter 2009

https://digitalcommons.wustl.edu/outlook/1178/thumbnail.jp

Sickle Cell Screening of College Athletes: Legal Obligations Fulfilled, Moral Obligations Lacking

30 page

Psychological Effects of False-Positive Results in Expanded Newborn Screening in China

Objectives: As more families participate expanded newborn screening for metabolic disorders in China, the overall number of false positives increases. Our goal was to assess the potential impact on parental stress, perceptions of the child’s health, and family relationships. Methods: Parents of 49 infants with false-positive screening results for metabolic disorders in the expanded newborn screening panel were compared with parents of 42 children with normal screening results. Parents first completed structured interview using likert scales, closed and open questions. Parents also completed the parenting stress index. Results: A total of 88 mothers and 41 fathers were interviewed. More mothers in the false-positive group reported that their children required extra parental care (21%), compared with 5 % of mothers in the normal-screened group (P,0.001). 39 % of mothers in the false-positive group reported that they worry about their child’s future development, compared with 10 % of mothers in the normal-screened group (P,0.001). Fathers in the false-positive group did not differ from fathers in the normal-screened group in reporting worry about their child’s extra care requirements, and their child’s future development. Children with false-positive results compared with children with normal results were triple as likely to experience hospitalization (27%vs 9%, respectively; P,0.001). Conclusions: The results showing false-positive screening results may affect parental stress and the parent-chil

Uued diagnoosimeetodid kaasasündinud ainevahetushaiguste varajaseks avastamiseks Eestis

Väitekirja elektrooniline versioon ei sisalda publikatsioonePärilikud ainevahetushaigused (AVH-d) on organismi biokeemilise tasakaalu häired, mida põhjustavad monogeensed geenimutatsioonid. Kuigi tegemist on kaasasündinud haigustega, puuduvad enamikul lastest sünnihetkel sümptomid, mis ilmnevad hiljem ja on sageli pöördumatud ning eluiga lühendavad. Sestap muutub järjest olulisemaks pärilike AVH varajane diagnostika, tagamaks asjakohane pere nõustamine, sünnieelne diagnostika ning võimalusel ka ravi. Sellest ajendatuna on vastsündinute sõeltestimise programmid pidevas muutumises, et tuvastada efektiivsemalt ravitavaid AVH-i asümptoomses perioodis. Kuid kahjuks pole kõik kaasasündinud AVH-d nagu mitokondriaalsed haigused (MH) sõeltestitavad ning molekulaarselt kinnitatud diagnoosini jõudmine on vahel väga keeruline, kuna kliinilised probleemid ja nende algusaeg on äärmiselt varieeruvad ka sama pere liikmete seas. Samas on üksikutes teadustöödes hakatud valitud patsientidel diagnoosi leidmiseks rakendama kogu eksoomi sekveneerimist, mis kliinilises töös on veel minimaalselt kasutust leidnud. Käesolevas uuringus töötati välja Eesti jaoks sobivaim vastsündinute laiendatud sõeltestimise meetod ja ülesehitus, mida rakendati 54 899 vastsündinul ning 29-l tuvastati pärilik AVH, seega on uuritavate haiguste esinemissagedus Eestis 1:1893. Enim diagnoositi kaasasündinud omandatud vitamiin B12 puudulikkust, mille esinemissagedus on 1:2959. Teisest doktoritöö osast järeldub, et kliinilises töös on kogu eksoomi sekveneerimine lapseeas alanud MH kahtlusega patsientidel efektiivne: 28-st 17-l tuvastati haigusseoselised geenimutatsioonid, seega on saagis väga kõrge – 61%. Ka töötati välja ning võeti kasutusele mtDNA analüüsimeetod standardsel kogu eksoomi sekveneerimisel. Töö teist osa ilmestavad kolm haigusjuhtu. Neist esimeses kirjeldati esmakordselt patsiente, kellel esinevad liitheterosügootsena mutatsioonid CACNA1A geenis. Teises kirjeldati esmakordselt uustekkest mutatsioon SLC25A4 geenis, mis põhjustab kolmanda, eelnevatest selgelt eristuva, kliinilise fenotüübi. Kolmandas presenteeriti patsiente uustekkese mutatsiooniga NDUFB11 geenis, mis põhjustab varieeruvat kliinilist fenotüüpi, kuid prevaleeruvad sümptomid on histiotsütoidne kardiomüopaatia ja kaasasündinud sideroblastne aneemia.Inborn errors of metabolism are monogenic disorders causing a biochemical imbalance in the organism. Although these disorders are congenital, the newborns are often symptom-free and signs of the disorder occur later, are often irreversible, and reduce lifespan. Therefore, an early diagnosis is imperative in order to provide appropriate family counseling, prenatal diagnosis and treatment. This has led to the continuous improvement of neonatal screening programs to identify disorders in the asymptomatic period. Unfortunately, newborn screening cannot identify all congenital metabolic disorders, such as mitochondrial disorders (MD). The molecularly confirmed diagnosis is often very difficult to achieve, as clinical problems and their onset are extremely variable, even among members of the family. Therefore, few research groups have implemented the whole exome sequencing (WES) in selected patients to reach the diagnosis, but this method has barely used in clinical practice. The current study clarifies the most suitable methodology and structure of the expanded newborn screening program for Estonia, which was applied to 54 899 newborns and 29 of them were identified with the congenital metabolic disorder. Therefore, the prevalence of the tested diseases is 1:1893 in Estonia. The most frequent diagnosis was congenital acquired vitamin B12 deficiency with prevalence of 1:2959. The second part of the dissertation evaluates the effectiveness of WES analysis in clinical practice in patients with suspicion of childhood-onset MD. Disease-causing gene variants were found in 17 out of 28 patients (61%). Furthermore, the analysis of mtDNA from standard WES reads was also worked out and implemented in clinical work. The second part of the work also includes three well-described patients, together with the investigations that have led to the first-ever description of compound heterozygous mutations in the CACNA1A gene; the discovery of a novel de novo mutation in the SLC25A4 gene, which causes the third distinct clinical phenotype associated with this gene; and the presentation of the novel mutation in the NDUFB11 gene along with the expansion of the variable clinical phenotype, although the predominant symptoms are histiocytoid cardiomyopathy and congenital sideroblastic anemia

Current issues in medically assisted reproduction and genetics in Europe: research, clinical practice, ethics, legal issues and policy. European Society of Human Genetics and European Society of Human Reproduction and Embryology.

In March 2005, a group of experts from the European Society of Human Genetics and European Society of Human Reproduction and Embryology met to discuss the interface between genetics and assisted reproductive technology (ART), and published an extended background paper, recommendations and two Editorials. Seven years later, in March 2012, a follow-up interdisciplinary workshop was held, involving representatives of both professional societies, including experts from the European Union Eurogentest2 Coordination Action Project. The main goal of this meeting was to discuss developments at the interface between clinical genetics and ARTs. As more genetic causes of reproductive failure are now recognised and an increasing number of patients undergo testing of their genome before conception, either in regular health care or in the context of direct-to-consumer testing, the need for genetic counselling and preimplantation genetic diagnosis (PGD) may increase. Preimplantation genetic screening (PGS) thus far does not have evidence from randomised clinical trials to substantiate that the technique is both effective and efficient. Whole-genome sequencing may create greater challenges both in the technological and interpretational domains, and requires further reflection about the ethics of genetic testing in ART and PGD/PGS. Diagnostic laboratories should be reporting their results according to internationally accepted accreditation standards (International Standards Organisation - ISO 15189). Further studies are needed in order to address issues related to the impact of ART on epigenetic reprogramming of the early embryo. The legal landscape regarding assisted reproduction is evolving but still remains very heterogeneous and often contradictory. The lack of legal harmonisation and uneven access to infertility treatment and PGD/PGS fosters considerable cross-border reproductive care in Europe and beyond. The aim of this paper is to complement previous publications and provide an update of selected topics that have evolved since 2005

Controlling sickle cell disease in Ghana - ethics and options

Sickle Cell Disease (SCD) is a significant public health burden in Ghana. Recent studies indicate that 2% of Ghanaian newborns are affected by SCD; one in three Ghanaians has the hemoglobin S and/or C gene. As a means of controlling the disease, some authorities have recommended prenatal diagnosis (PND) and selective abortion. In the current era, SCD has a good prognosis and fairly reasonable quality of life. Advances in bone marrow transplantation have shown the disease is curable in selected patients. PND and selective abortion therefore raises a myriad of ethical dilemmas which are considered in this review. In the light of the demonstration of improved prognosis in recent times, PND and selective abortion appears to be applying capital punishment to the unborn child for “crimes” only the parents can be responsible for. In this review, we recommend control of SCD on three levels – preconception genetic testing and strategic reproductive choices, PND and education for carrier parents, and holistic management of persons with SCD. We emphasize the critical importance of self-management, especially self-awareness, in assuring a good quality of life for persons with SCD. We believe such an approach is cost-effective, and consistent with sound ethical principles and good conscience

Newsletter, 2003-09, no. 27

The newsletter contains both association business and material of interest to midwives and related health care workers.The Association's name has changed several times based on the newsletter: from January 1992 - January 1997 it was The Alliance of Nurse-Midwives, Maternity and Neonatal Nurses, dropping the "Nurse-" after July 1994; from March 1997 - September 2000 it was Newfoundland and Labrador Midwives Association, and the issue numbering was reset; and in January 2001 it became Association of Midwives of Newfoundland and Labrador