How Many People Have a Huntington's Disease Expansion: A Population-Based Prevalence Study in Northern Scotland.

Introduction: Previous work demonstrated a prevalence of 14.6 per 100,000 manifest Huntington's disease (HD) patients and 8.3 per 100,000 identified pre-symptomatic gene expansion carriers (IPGEC) in Northern Scotland.

Should Scotland provide genome-wide sequencing for the diagnosis of rare developmental disorders? A cost-effectiveness analysis.

Aims: This study aims to evaluate the cost effectiveness of genetic and genomic testing strategies for the diagnosis of rare developmental disorders in NHS Scotland.

Methods: Six genetic and genomic testing strategies were evaluated using a decision tree model. First-line, second-line and last-resort trio genome sequencing (GS), and second-line and last-resort trio exome sequencing (ES) were compared with standard genetic testing.

Methods applied to neonatal dried blood spot samples for secondary research purposes: a scoping review.

This scoping review aimed to synthesize the analytical techniques used and methodological limitations encountered when undertaking secondary research using residual neonatal dried blood spot (DBS) samples. Studies that used residual neonatal DBS samples for secondary research (i.e.

Alternative cascade-testing protocols for identifying and managing patients with familial hypercholesterolaemia: systematic reviews, qualitative study and cost-effectiveness analysis.

Background: Cascade testing the relatives of people with familial hypercholesterolaemia is an efficient approach to identifying familial hypercholesterolaemia. The cascade-testing protocol starts with identifying an index patient with familial hypercholesterolaemia, followed by one of three approaches to contact other relatives: indirect approach, whereby index patients contact their relatives; direct approach, whereby the specialist contacts the relatives; or a combination of both direct and indirect approaches. However, it is unclear which protocol may be most effective.

VIKING II, a worldwide observational cohort of volunteers with northern isles ancestry.

Introduction: The purpose of VIKING II is to create an observational cohort of volunteers with ancestry from the Northern Isles of Scotland, primarily for identifying genetic variants influencing disease. The new online protocol is separate to, but follows on from, earlier genetic epidemiological clinic-based studies in the isolated populations of Orkney and Shetland. These populations are favourable for the study of rarer genetic variants due to genetic drift, the large number of relatives, and availability of pedigree information.

Severe Hypertriglyceridaemia and Chylomicronaemia Syndrome-Causes, Clinical Presentation, and Therapeutic Options.

We have reviewed the genetic basis of chylomicronaemia, the difference between monogenic and polygenic hypertriglyceridaemia, its effects on pancreatic, cardiovascular, and microvascular complications, and current and potential future pharmacotherapies. Severe hypertriglyceridaemia (TG > 10 mmol/L or 1000 mg/dL) is rare with a prevalence of <1%. It has a complex genetic basis.

Clinical case study meets population cohort: identification of a BRCA1 pathogenic founder variant in Orcadians.

We multiply ascertained the BRCA1 pathogenic missense variant c.5207T > C; p.Val1736Ala (V1736A) in clinical investigation of breast and ovarian cancer families from Orkney in the Northern Isles of Scotland, UK.

Understanding how educational interventions improve treatment adherence in patients with familial hypercholesterolaemia: a systematic review.

Effective treatments for familial hypercholesterolaemia (FH) offer patients the opportunity of normal life expectancy, but lifelong adherence to both lipid-lowering therapies and lifestyle measures is challenging, and thus, this is rarely achieved. The aim of this systematic review is to identify attributes of educational interventions that promote adherence to treatment in FH. A systematic literature search was undertaken using Medline, CINAHL, HMIC and Embase.

Feasibility and ethics of using data from the Scottish newborn blood spot archive for research.

Background: Newborn heel prick blood spots are routinely used to screen for inborn errors of metabolism and life-limiting inherited disorders. The potential value of secondary data from newborn blood spot archives merits ethical consideration and assessment of feasibility for public benefit. Early life exposures and behaviours set health trajectories in childhood and later life.

Germline intergenic duplications at Xq26.1 underlie Bazex-Dupré-Christol basal cell carcinoma susceptibility syndrome.

Background: Bazex-Dupré-Christol syndrome (BDCS; MIM301845) is a rare X-linked dominant genodermatosis characterized by follicular atrophoderma, congenital hypotrichosis and multiple basal cell carcinomas (BCCs). Previous studies have linked BDCS to an 11·4-Mb interval on chromosome Xq25-q27.1.

Evaluation of tumour surveillance protocols and outcomes in von Hippel-Lindau disease in a national health service.

Background: Von Hippel-Lindau (VHL) disease is an inherited tumour predisposition syndrome and a paradigm for the importance of early diagnosis and surveillance. However, there is limited information on the "real world" management of VHL disease.

Methods: A national audit of VHL disease in the United Kingdom.

Continuing the sequence? Towards an economic evaluation of whole genome sequencing for the diagnosis of rare diseases in Scotland.

Novel developments in genomic medicine may reduce the length of the diagnostic odyssey for patients with rare diseases. Health providers must thus decide whether to offer genome sequencing for the diagnosis of rare conditions in a routine clinical setting. We estimated the costs of singleton standard genetic testing and trio-based whole genome sequencing (WGS), in the context of the Scottish Genomes Partnership (SGP) study.

Creation and Worldwide Utilisation of New COVID-19 Online Information Hub for Genetics Health Professionals, Patients and Families.

The current COVID-19 pandemic has unfortunately resulted in many significant concerns for individuals with genetic disorders and their relatives, regarding the viral infection and, particularly, its specific implications and additional advisable precautions for individuals affected by genetic disorders. To address this, the resulting requirement for guidance and information for the public and for genetics professionals was discussed among colleagues nationally, on the ScotGEN Steering Committee, and internationally on the Education Committee of the European Society of Human Genetics (ESHG). It was agreed that the creation of an online hub of genetics-related COVID-19 information resources would be particularly helpful.

The known burden of Huntington disease in the North of Scotland: prevalence of manifest and identified pre-symptomatic gene expansion carriers in the molecular era.

Background: Huntington disease prevalence was first estimated in Grampian, northern Scotland in 1984. Molecular testing has since increased ascertainment.

Objective: To estimate the prevalence of manifest Huntington disease and identified pre-symptomatic gene expansion carriers (IPGEC) in northern Scotland, and estimate the magnitude of biases in prevalence studies that rely upon routine coding in primary care records.

Young-onset colorectal cancer in the North East of Scotland: survival, clinico-pathological features and genetics.

Background: Colorectal cancer (CRC) in patients aged under 55 years is on the rise, constituting approximately 10% of cases. Our aim was to determine the survival and clinico-pathological details of young-onset CRC (yCRC), as well as audit the referral rate to genetic services and thus establish the incidence of inherited cancer syndromes.

Methods: A retrospective case note review was conducted for patients aged under 55 years who were diagnosed with CRC between 2005 and 2015 in the North East of Scotland.

Genetics professionals' experiences of facilitating parent/child communication through the genetic clinic.

While guidelines advise genetic health professionals to support and encourage family communication about genetic risk, there can be professional uncertainty when advising parents about communication with children. We sought to explore genetic health professionals' views and experiences of facilitating parent/child communication in clinical practice, particularly in relation to adult-onset inherited conditions. Twenty-three in-depth interviews were conducted with United Kingdom genetic health professionals.

An actionable KCNH2 Long QT Syndrome variant detected by sequence and haplotype analysis in a population research cohort.

The Viking Health Study Shetland is a population-based research cohort of 2,122 volunteer participants with ancestry from the Shetland Isles in northern Scotland. The high kinship and detailed phenotype data support a range of approaches for associating rare genetic variants, enriched in this isolate population, with quantitative traits and diseases. As an exemplar, the c.

A case-note review of continued pregnancies found to be at a high risk of Huntington's disease: considerations for clinical practice.

Huntington's disease (HD) is a severe neurodegenerative condition that impacts the whole family. Prenatal diagnosis by direct or exclusion testing is available for couples at risk of transmitting HD to their children. An ethical problem can arise after prenatal diagnosis for HD if a known 'high risk' pregnancy is continued to term: international guidelines emphasise that this situation should be avoided where possible, as it removes the resulting child's future right to make an informed, autonomous decision about predictive testing.

27 years of prenatal diagnosis for Huntington disease in the United Kingdom.

Purpose: There is little long-term, population-based data on uptake of prenatal diagnosis for Huntington disease (HD), a late-onset autosomal dominant neurodegenerative disorder, and the effect of the availability of preimplantation genetic diagnosis (PGD) on families' decisions about conventional prenatal diagnosis is not known. We report trends in prenatal diagnosis and preimplantation diagnosis for HD in the United Kingdom since services commenced.

Methods: Long-term UK-wide prospective case record-based service evaluation in 23 UK Regional Genetic Centres 1988-2015, and four UK PGD centers 2002-2015.

Parents' views of genetic testing and treatment of familial hypercholesterolemia in children: a qualitative study.

Familial hypercholesterolemia (FH) is a serious inherited disorder, which greatly increases individuals' risk of cardiovascular disease (CVD) in adult life. However, medical treatment and lifestyle adjustments can fully restore life expectancy. Whilst European guidance advises that where there is a known family mutation genetic testing is undertaken in early childhood, the majority of the at-risk population remain untested and undiagnosed.