Notkun rafrænna gagnagrunna í krabbameinserfðaráðgjöf

The overall aim of this PhD thesis was to cohesively assess the availability and use of electronic genealogy databases and information from cancer registries to construct electronically generated pedigrees for risk assessment in genetic counselling. The thesis is built upon three published papers. Hereditary breast and ovarian cancer (HBOC), due to the Icelandic founder BRCA2 PV was used as an example. A second objective was to determine the optimal size of pedigrees for risk assessment in cancer genetic counselling. Three different approaches were used. Study I was a systematic literature review for articles describing the use of electronic genealogy and cancer databases in clinical service. Key findings: Published data on the use of such databases was limited, and the search identified only four articles fitting the search terms. Two of the papers were discussion papers. One of the four articles described an Icelandic study which applied information from the Genetical Committee of the University of Iceland. Study II was qualitative, on the experience of counsellees where electronically generated pedigrees (EGPs) were used in hereditary breast and ovarian cancer (HBOC) genetic counselling. Data was collected via an online focus group using an online discussion board. In genetic counselling, family health and genealogical history are collected to assess risk and clarify the inheritance mode of a suspected or known disorder. Key findings: Prior to genetic counselling, the majority of participants said that they had known about genetic counselling, and the most common reason for GC was a strong family history of cancer. Most participants were positive towards the use of electronic pedigrees and had trust in both the professionals and the information from the databases used to generate the pedigrees. Some, however, worried that insurance companies would obtain the information from the databases and possibly raise premiums or even deny insurance outright based on the information. Laws against genetic discrimination and the protection of personal data exist, both in health insurance and employment. The majority of participants had either unchanged or better family communication following genetic counselling. As relatives may have a diverse reaction to the offer of genetic testing, good family communication is essential. In Study III, the clinical use of electronically generated pedigrees was assessed, and the optimal pedigree size was calculated. Key findings: Using EGPs for risk assessment in cancer genetic counselling enabled accurate and comprehensive risk assessment in HBOC families. Further, such use is cost-effective and reduces work. We used Receiver Operation Curves (ROC) and C-statistics based on pair-wise comparison to evaluate the effect of pedigree size on the prediction of the presence of the Icelandic founder BRCA2 PV. Optimal results were attained using pedigrees with 3° relatives. Adding 4° relatives did not improve the outcome. Obtaining informed consent for the construction of pedigrees was straightforward, and no breaches of security (i.e. leakage of classified or restricted information) were observed. Conventional methods of collecting and constructing large enough pedigrees are time-consuming and difficult compared to our approach. This thesis reflects the experience of a clinical genetic service using electronically generated pedigrees in clinical practice. This approach is well established in Iceland and has been used for over 13 years in cancer genetic counselling. It is efficient and without complications such as breach of data and mistrust on behalf of the counsellees. A significant result from this work is that the optimal size of cancer pedigree, 3° pedigree which can take up to five generations. Such a pedigree is very difficult and impractical to generate using the conventional handmade technique. This should create a motive to use EGPs in other countries where some or all the resources are readily available

A population-based survey of FBN1 variants in Iceland reveals underdiagnosis of Marfan syndrome

Publisher Copyright: © 2023, The Author(s).Marfan syndrome (MFS) is an autosomal dominant condition characterized by aortic aneurysm, skeletal abnormalities, and lens dislocation, and is caused by variants in the FBN1 gene. To explore causes of MFS and the prevalence of the disease in Iceland we collected information from all living individuals with a clinical diagnosis of MFS in Iceland (n = 32) and performed whole-genome sequencing of those who did not have a confirmed genetic diagnosis (27/32). Moreover, to assess a potential underdiagnosis of MFS in Iceland we attempted a genotype-based approach to identify individuals with MFS. We interrogated deCODE genetics’ database of 35,712 whole-genome sequenced individuals to search for rare sequence variants in FBN1. Overall, we identified 15 pathogenic or likely pathogenic variants in FBN1 in 44 individuals, only 22 of whom were previously diagnosed with MFS. The most common of these variants, NM_000138.4:c.8038 C > T p.(Arg2680Cys), is present in a multi-generational pedigree, and was found to stem from a single forefather born around 1840. The p.(Arg2680Cys) variant associates with a form of MFS that seems to have an enrichment of abdominal aortic aneurysm, suggesting that this may be a particularly common feature of p.(Arg2680Cys)-associated MFS. Based on these combined genetic and clinical data, we show that MFS prevalence in Iceland could be as high as 1/6,600 in Iceland, compared to 1/10,000 based on clinical diagnosis alone, which indicates underdiagnosis of this actionable genetic disorder.Peer reviewe

Recontacting patients in clinical genetics services: recommendations of the European Society of Human Genetics

Technological advances have increased the availability of genomic data in research and the clinic. If, over time, interpretation of the significance of the data changes, or new information becomes available, the question arises as to whether recontacting the patient and/or family is indicated. The Public and Professional Policy Committee of the European Society of Human Genetics (ESHG), together with research groups from the UK and the Netherlands, developed recommendations on recontacting which, after public consultation, have been endorsed by ESHG Board. In clinical genetics, recontacting for updating patients with new, clinically significant information related to their diagnosis or previous genetic testing may be justifiable and, where possible, desirable. Consensus about the type of information that should trigger recontacting converges around its clinical and personal utility. The organization of recontacting procedures and policies in current health care systems is challenging. It should be sustainable, commensurate with previously obtained consent, and a shared responsibility between healthcare providers, laboratories, patients, and other stakeholders. Optimal use of the limited clinical resources currently available is needed. Allocation of dedicated resources for recontacting should be considered. Finally, there is a need for more evidence, including economic and utility of information for people, to inform which strategies provide the most cost-effective use of healthcare resources for recontacting

Kynningarmál ferðaþjónustufyrirtækja í Eyjafirði : menning og ímynd

Verkefnið er opið nemendum og starfsfólki Háskólans á AkureyriMarkmiðið með þessu verkefni er að kanna hvernig ferðaþjónustufyrirtæki Eyjafjarðarsvæðinu eru að koma sér á framfæri og hvort þau eru að kynna menningu og ímynd svæðisins. Þar sem ferðaþjónustufyrirtæki í Eyjafirði eru jafn misjöfn eins og þau eru mörg þá var búist við því að misjafnlega væri að kynningarmálum staðið. Farið var í ítarlega greiningu á svæðinu í heild svo sem SVÓT – greiningu og einnig var farið í að skoða fyrirtæki í ferðaþjónustu. Aflað var heimilda og mat lagt á efnið og komist var að eftirfarandi niðurstöðu: Kynningarmál eru mjög misjöfn, það fer eftir stærð og umfangi fyrirtækis hversu mikið er lagt í markaðsstarfið. Eftir því sem fyrirtækin eru smærri er minna lagt í kynningarmál og sum þeirra láta jafnvel nægja að nota bækling og smáauglýsingu í símaskránni. Aftur á móti eru stærri fyrirtæki að gera meira í markaðssetningu hjá sér og taka sig jafnvel nokkur saman til að ná til stærri markhóps. Stærri fyrirtæki eru með fastmótaðri kynningaráætlun en þau minni. Að mati forsvarsmanna þeirra fyrirtækja sem talað var við, kom sterklega í ljós munur á stærri og minni fyrirtækjum í sambandi við hvort auglýsingar skili árangri. Stærri fyrirtæki sem leggja meira í auglýsingar og kynningarmál telja að auglýsingar skili þeim árangri sem leitað er eftir en smærri fyrirtækin telja að auglýsingar skili litlum eða engum árangri það sé nóg að vera í einhverjum bæklingum og í símaskránni. Milli stærðin vildi meina að halda úti góðri heimasíðu væri það sem skilaði mestum árangri. Fyrirtæki eru ekki að koma menningu og ímynd svæðisins á framfæri nema það tengist beint þeirra rekstri, þó er undantekning þegar fyrirtæki taka sig saman í kynningarmálum þá er vísir að því að menningu og ímynd séu gerð skil. Lykilorð: • Eyjafjörður. • Ferðaþjónusta. • Kynningarmál. • Menning. • Ímynd

Women´s preferences for prenatal tests A discrete choice experiment to contrast noninvasive prenatal testing with current invasive tests

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.Inngangur: Í þróun hefur verið ný tegund fósturskimunar sem felur í sér að tekin er blóðprufa úr móðurinni og óbundið erfðaefni fóstursins skoðað í móðurblóði. Tilgangur rannsóknarinnar var að skoða hvaða þættir fósturgreiningar eru mikilvægastir að mati barnshafandi kvenna og heilbrigðisstarfsmanna hér á landi. Efniviður og aðferðir: Stuðst var við valkostasnið (discrete choice experimental design) í rannsókninni. Spurningalisti var annars vegar afhentur barnshafandi konum í meðgönguvernd á heilsugæslustöðvum höfuðborgarsvæðisins og hins vegar sendur rafrænt á heilbrigðisstarfsmenn. Þýðið var allar barnshafandi konur sem voru í meðgönguvernd frá júní til nóvember 2014 og allir heilbrigðisstarfsmenn sem sinna konum á meðgöngu hér á landi. Í úrtaki voru 300 barnshafandi konur sem komnar voru 20 vikur eða lengra í meðgöngu og allir heilbrigðisstarfsmenn sem sinna konum á meðgöngu. Úrtakið var hentugleikaúrtak og þeim konum boðin þátttaka sem höfðu annaðhvort valið að fara ekki í fósturskimun við 11-14 vikur eða fengið niðurstöðu um litlar líkur á litningagöllum. Niðurstöður: Barnshafandi konur og heilbrigðisstarfsmenn vilja rannsókn sem er nákvæm og örugg fyrir fóstrið, framkvæmd snemma á meðgöngu og gefur ítarlegar upplýsingar. Í samanburði við heilbrigðisstarfsmenn sem svöruðu spurningalistanum (20,8% svarhlutfall, 61/293) voru barnshafandi konur (62% svarhlutfall, 186/300) tilbúnar til að bíða lengur og sætta sig við minni nákvæmni fyrir rannsókn sem hafði enga hættu á fósturláti í för með sér. Ályktun: Sambærilegar niðurstöður má sjá í nokkrum erlendum rannsóknum en mikilvægt er að afla vitneskju um viðhorf barnshafandi kvenna og heilbrigðisstarfsmanna áður en ný tegund fósturskimunar er tekin upp hér á landi. Góð ráðgjöf er mikilvæg til að tryggja að konur skilji alla þætti rannsóknarinnar og eigi þannig möguleika á að taka upplýsta ákvörðunIntroduction: Prenatal screening in early pregnancy is offered to all women in Iceland. In the case of an increased risk, invasive diagnostic test with 1% risk of fetal loss is offered. Recent developments include an exploration of a cell free fetal DNA in maternal plasma. The aim of this study was to explore factors that are of importance to pregnant women and professionals in fetal diagnosis. Material and methods: A questionnaire incorporating a discrete choice experimental design was used. The population included all pregnant women attending antenatal care in the capital area from June to November 2014 and all health professionals provide prenatal care in Iceland. We included all health professionals who provide prenatal care and a convenience sample of 300 pregnant women attending primary health clinics, who were more than 20 weeks pregnant, had declined screening or had low risk result. Results: Overall pregnant women and professionals prefer a test which is accurate and safe, performed early in pregnancy and provides thorough information. In comparison with the health professionals, who responded to the questionnaire (20,8%, 61/293), the pregnant women placed greater emphasis on test safety and comprehensive information but less on accuracy and early testing. Conclusion: Similar results can be found in other studies but it is of importance to gain knowledge of pregnant women´s and professionals views before a new method in screening contexts is implimented in Iceland. Good counseling is of importance to ensure that women understand all aspects of the technique which increases informed choices. Key words: non-invasive prenatal testing (NIPT); Down syndrome; discrete choice experiment; women’s preferences; health professionals’ attitude

Increased use of genetic health care in Iceland 2012-2017

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadINNGANGUR Formleg erfðaráðgjafareining hefur verið starfrækt á Landspítala við Hringbraut frá árinu 2006. Samhliða hefur áhugi og þörf á erfðalæknisfræði í almennri heilbrigðisþjónustu aukist til muna. Í þessari grein er starfsemi og útkoma erfðarannsókna hjá erfða- og sameindalæknisfræðideild Landspítala á 5 ára tímabili (2012-2017) tekin saman. Sérstaklega var horft til fjölda einstaklinga, ástæðu komu, ástæðu erfðarannsókna án aðkomu erfðaráðgjafar Landspítala og eins var nýtni (heildarhlutfall rannsókna sem skila jákvæðri niðurstöðu) erfðarannsókna skoðuð. AÐFERÐIR Gögn um komur voru fengin upp úr sjúkraskrárkerfi erfðaráðgjafar, Shire og Sögu/Heilsugátt. NIÐURSTAÐA Fjöldi þeirra sem sóttu þjónustu erfðaráðgjafareiningarinnar jókst árlega allt tímabilið. Ástæður fyrir erfðaráðgjöf reyndust vera krabbameinstengdar í tveimur þriðju hlutum tilfella. Aðrir komu vegna fjölskyldulægra sjúkdóma sem eru algengir á Íslandi, ýmist sjúkdóma sem erfast ríkjandi (dæmi: vöðvaspennuvisnun og ofvaxtarhjartavöðvasjúkdómur) eða vegna víkjandi sjúkdóma (dæmi: mænuvöðvarýrnun og GM1-ganglio-síðkvilli). Algengast var að fólk færi í erfðarannsókn án aðkomu erfðaráðgjafar Landspítala vegna meðhöndlanlegra sjúkdóma, svo sem arfgengrar járnofhleðslu og bláæðasegatilhneigingar. Nýtni erfðarannsókna var metin fyrir a) leit að þekktum meinvaldandi breytingum, b) leit að meinvaldandi breytingum í stökum genum (eingenarannsóknir), c) fjölgenarannsóknir og d) tákn- og heilerfðamengisrannsóknir. Leit að þekktri breytingu skilaði jákvæðri niðurstöðu í 33% tilvika og leit í stöku geni í 46% tilvika. Nýtni fjölgenarannsókna vegna krabbameina var lægri (20%) samanborið við aðrar fjölgenarannsóknir (40%). Þá var nýtni tákn- og heilerfðamengisrannsókna 46%.INTRODUCTION: A genetic counselling unit at Landspitali hospital (LSH) was established in 2006. Meanwhile, genetic testing has become an integral part of general health care. In this article we detail the outcome of genetic testing at the Department of Genetic and Molecular Medicine (DGM) at Landspitali over a five year period (2012-2017). Factors that were analyzed for the time period were: Number of patients, reason for referral, reason for genetic testing without genetic counselling and yield (proportion of positive tests) of genetic testing. METHODS: Data was analysed from two medical record databases, Shire and Saga, used by the DGM in the time period. RESULTS: The number of individuals coming for genetic counselling increased every year over the time period. Reasons for referral were cancer-related in two-thirds of cases. Other reasons for referral included various other familial disorders. Most common were autosomal dominant disorders like myotonic dystrophy, hypertrophic cardiomyopathy and autosomal recessive disorders like spinal muscular atrophy (SMA) and GM1- gangliosidosis. Most common reasons for genetic testing outside of the LSH GC unit was because of managable diseases like hemochromatosis and F5/Prothrombin-related thrombophilia. Yield of genetic testing was assessed for a) known mutation testing / carrier testing, b) single gene testing, c) gene panel testing and d) whole genome and whole exome sequencing. Known mutation testing was positive in 33% of cases and single gene testing in 46% of cases. The yield of gene panel testing for cancer was found to be lower (20%) than gene panel testing for other disorders (40%). The yield of whole exome and whole genome sequencing was 46%