A cumulative impact assessment on the marine capacity to supply ecosystem services.

Ecosystem services link the status of biodiversity and its functioning to societal goods and benefits contributing to human wellbeing. As such, they can play a key role in preserving the environment and managing natural resources and ecosystems to conserve nature's contributions to people. Identification of the main threats acting on the natural environment, and how these may impact its capacity to supply ecosystem services, is fundamental to the maintenance of these services.

A roadmap towards quantitative cumulative impact assessments: Every step of the way.

Currently most Cumulative Impacts Assessments (CIAs) are risk-based approaches that assess the potential impact of human activities and their pressures on the ecosystem thereby compromising the achievement of policy objectives. While some of these CIAs apply actual data (usually spatial distributions) they often have to rely on categorical scores based on expert judgement if they actually assess impact which is often expressed as a relative measure that is difficult to interpret in absolute terms. Here we present a first step-wise approach to conduct a fully quantitative CIA based on the selection and subsequent application of the best information available.

A de novo Novel Splice Variant in an Adult Female with Severe Intellectual Disability.

The catenin beta-1 () gene, encoding a sub-unit of the cadherin/catenin protein complex that is involved in the Wnt signalling pathway important for proper interneuron development, is considered to be causative for the rare autosomal dominant mental retardation syndrome, formerly called MRD19 but later renamed neurodevelopmental disorder with spastic diplegia and visual defects (NEDSDV). Its main characteristics are moderate to severe intellectual disability (ID), disruptive autistic behaviours, microcephaly, absent or limited speech, facial dysmorphisms, peripheral hypertonia/spasticity, motor delay and visual defects. So far, 35 patients have been reported with a de novo loss-of-function variant in .

An integrated risk-based assessment of the North Sea to guide ecosystem-based management.

This study provides an integrated perspective to ecosystem based management (EBM) by considering a diverse array of societal goals, i.e. sustainable food supply, clean energy and a healthy marine ecosystem, and a selection of management measures to achieve them.

Toward a harmonized approach for environmental assessment of human activities in the marine environment.

With a foreseen increase in maritime activities, and driven by new policies and conventions aiming at sustainable management of the marine ecosystem, spatial management at sea is of growing importance. Spatial management should ensure that the collective pressures caused by anthropogenic activities on the marine ecosystem are kept within acceptable levels. A multitude of approaches to environmental assessment are available to provide insight for sustainable management, and there is a need for a harmonized and integrated environmental assessment approach that can be used for different purposes and variable levels of detail.

Long-QT mutation p.K557E-Kv7.1: dominant-negative suppression of IKs, but preserved cAMP-dependent up-regulation.

Aims: Mutations in KCNQ1, encoding for Kv7.1, the α-subunit of the IKs channel, cause long-QT syndrome type 1, potentially predisposing patients to ventricular tachyarrhythmias and sudden cardiac death, in particular, during elevated sympathetic tone. Here, we aim at characterizing the p.

Arrhythmogenic right ventricular dysplasia/cardiomyopathy according to revised 2010 task force criteria with inclusion of non-desmosomal phospholamban mutation carriers.

Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is frequently associated with desmosomal mutations. However, nondesmosomal mutations may be involved. The aim of this study was to assess the contribution of a phospholamban (PLN) gene mutation to ARVD/C diagnosis according to the revised 2010 task force criteria (TFC).

Recurrent and founder mutations in the Netherlands: cardiac Troponin I (TNNI3) gene mutations as a cause of severe forms of hypertrophic and restrictive cardiomyopathy.

Background: About 2-7% of familial cardiomyopathy cases are caused by a mutation in the gene encoding cardiac troponin I (TNNI3). The related clinical phenotype is usually severe with early onset. Here we report on all currently known mutations in the Dutch population and compared these with those described in literature.

Recurrent and Founder Mutations in the Netherlands: the Long-QT Syndrome.

BACKGROUND AND OBJECTIVE: The long-QT syndrome (LQTS) is associated with premature sudden cardiac deaths affecting whole families and is caused by mutations in genes encoding for cardiac proteins. When the same mutation is found in different families (recurrent mutations), this may imply either a common ancestor (founder) or multiple de novo mutations. We aimed to review recurrent mutations in patients with LQTS.

Recurrent and founder mutations in the Netherlands : Plakophilin-2 p.Arg79X mutation causing arrhythmogenic right ventricular cardiomyopathy/dysplasia.

Background: Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is an inherited cardiac disease with reduced penetrance and a highly variable expression. Mutations in the gene encoding the plakophilin-2 gene (PKP2) are detected in about 50% of ARVC/D patients. The p.

Founder mutations in hypertrophic cardiomyopathy patients in the Netherlands.

In this part of a series on cardiogenetic founder mutations in the Netherlands, we review the Dutch founder mutations in hypertrophic cardiomyopathy (HCM) patients. HCM is a common autosomal dominant genetic disease affecting at least one in 500 persons in the general population. Worldwide, most mutations in HCM patients are identified in genes encoding sarcomeric proteins, mainly in the myosin-binding protein C gene (MYBPC3, OMIM #600958) and the beta myosin heavy chain gene (MYH7, OMIM #160760).

Desmoglein-2 and desmocollin-2 mutations in dutch arrhythmogenic right ventricular dysplasia/cardiomypathy patients: results from a multicenter study.

Background: This study aimed to evaluate the prevalence and type of mutations in the major desmosomal genes, Plakophilin-2 (PKP2), Desmoglein-2 (DSG2), and Desmocollin-2 (DSC2), in arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) patients. We also aimed to distinguish relevant clinical and ECG parameters.

Methods And Results: Clinical evaluation was performed according to the Task Force Criteria (TFC).

A genetic variants database for arrhythmogenic right ventricular dysplasia/cardiomyopathy.

Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is a hereditary cardiomyopathy characterized by fibrofatty replacement of cardiomyocytes, ventricular tachyarrhythmias and sudden death. ARVD/C is mainly caused by mutations in genes encoding desmosomal proteins. However, the pathogenicity of variants is not always clear.

Defective complex I assembly due to C20orf7 mutations as a new cause of Leigh syndrome.

Background: Leigh syndrome is an early onset, progressive, neurodegenerative disorder with developmental and motor skills regression. Characteristic magnetic resonance imaging abnormalities consist of focal bilateral lesions in the basal ganglia and/or the brainstem. The main cause is a deficiency in oxidative phosphorylation due to mutations in an mtDNA or nuclear oxidative phosphorylation gene.

Subepicardial phase 0 block and discontinuous transmural conduction underlie right precordial ST-segment elevation by a SCN5A loss-of-function mutation.

Two mechanisms are generally proposed to explain right precordial ST-segment elevation in Brugada syndrome: 1) right ventricular (RV) subepicardial action potential shortening and/or loss of dome causing transmural dispersion of repolarization; and 2) RV conduction delay. Here we report novel mechanistic insights into ST-segment elevation associated with a Na(+) current (I(Na)) loss-of-function mutation from studies in a Dutch kindred with the COOH-terminal SCN5A variant p.Phe2004Leu.

A single hERG mutation underlying a spectrum of acquired and congenital long QT syndrome phenotypes.

The long QT syndrome (LQTS) is a multi-factorial disorder that predisposes to life-threatening arrhythmias. Both hereditary and acquired subforms have been identified. Here, we present clinical and biophysical evidence that the hERG mutation c.

[Genetic identification of patients and families with a long-QT syndrome: large regional differences in the result of 10 years].

Objective: To determine the pattern of referral of Dutch patients with a long-QT syndrome (LQTS) on the basis of the postal codes of the LQTS probands from whom blood samples were submitted for DNA diagnostics.

Design: . Retrospective cohort study.

Mapping a novel locus for familial atrial fibrillation on chromosome 10p11-q21.

Background: Atrial Fibrillation (AF), the most common cardiac arrhythmia, is a significant public health problem in the United States, affecting approximately 2.2 million Americans. Recently, several chromosomal loci and genes have been found to be associated with familial AF.

Chip-based mtDNA mutation screening enables fast and reliable genetic diagnosis of OXPHOS patients.

Purpose: Oxidative phosphorylation is under dual genetic control of the nuclear and the mitochondrial DNA (mtDNA). Oxidative phosphorylation disorders are clinically and genetically heterogeneous, which makes it difficult to determine the genetic defect, and symptom-based protocols which link clinical symptoms directly to a specific gene or mtDNA mutation are falling short. Moreover, approximately 25% of the pediatric patients with oxidative phosphorylation disorders is estimated to have mutations in the mtDNA and a standard screening approach for common mutations and deletions will only explain part of these cases.

Plakophilin-2 mutations are the major determinant of familial arrhythmogenic right ventricular dysplasia/cardiomyopathy.

Background: Mutations in the plakophilin-2 gene (PKP2) have been found in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVC). Hence, genetic screening can potentially be a valuable tool in the diagnostic workup of patients with ARVC.

Methods And Results: To establish the prevalence and character of PKP2 mutations and to study potential differences in the associated phenotype, we evaluated 96 index patients, including 56 who fulfilled the published task force criteria.

Long QT syndrome caused by a large duplication in the KCNH2 (HERG) gene undetectable by current polymerase chain reaction-based exon-scanning methodologies.

Background: The numerous mutations in the long QT syndrome (LQTS)-associated genes reported to date are point mutations or small insertions and deletions in coding regions or at splice junctions.

Objectives: The purpose of this study was to determine the relative copy number of gene exons in a series of mutation-negative LQTS probands.

Methods: We used a quantitative multiplex approach because the polymerase chain reaction (PCR)-based exon-scanning methodologies routinely utilized in mutation analysis are unable to detect large genomic alterations.

HERG mutation predicts short QT based on channel kinetics but causes long QT by heterotetrameric trafficking deficiency.

Objective: Mutations in the KCNH2 (hERG, human ether-à-go-go related gene) gene may cause a reduction of the delayed rectifier current I(Kr), thereby leading to the long QT syndrome (LQTS). The reduced I(Kr) delays the repolarisation of cardiac cells and renders patients vulnerable to ventricular arrhythmias and sudden death. We identified a novel mutation in a LQTS family and investigated its functional consequences using molecular and microscopic techniques.

Novel mutation in the Per-Arnt-Sim domain of KCNH2 causes a malignant form of long-QT syndrome.

Background: It has been proposed that the highest risk for cardiac events in patients with long-QT syndrome subtype 2 (LQT2) is related to mutations in the pore region of the KCNH2 channel. It has also been suggested that a subpopulation of LQT2 patients may benefit from pharmacological therapy with modified KCNH2 channel-blocking drugs.

Methods And Results: In a large LQT2 family (n=33), we have identified a novel nonpore missense mutation (K28E) in the Per-Arnt-Sim (PAS) domain of the KCNH2 channel associated with a malignant phenotype: One third of the suspected gene carriers experienced a major cardiac event.

Methods in molecular cardiology: DHPLC mutation detection analysis.

An increasing number of mutations have been identified in genes involved in cardiac disorders which has led to novel insights in the pathophysiology of inherited cardiac diseases. As a result of these findings, techniques specialised in automated high-throughput analysis are implemented to handle the increasing number of diagnostic genetic requests. Denaturing high-performance liquid chromatography (DHPLC) is one such novel technique that fulfils the criteria of speed, sensitivity and accuracy.