Some individuals with a particular disease-causing mutation or genotype fail to express most if not all features of the disease in question, a phenomenon that is known as ‘reduced (or incomplete) penetrance’. Reduced penetrance is not uncommon; indeed, there are many known examples of ‘disease-causing mutations’ that fail to cause disease in at least a proportion of the individuals who carry them. Reduced penetrance may therefore explain not only why genetic diseases are occasionally transmitted through unaffected parents, but also why healthy individuals can harbour quite large numbers of potentially disadvantageous variants in their genomes without suffering any obvious ill effects. Reduced penetrance can be a function of the specific mutation(s) involved or of allele dosage. It may also result from differential allelic expression, copy number variation or the modulating influence of additional genetic variants in cis or in trans. The penetrance of some pathogenic genotypes is known to be age- and/or sex-dependent. Variable penetrance may also reflect the action of unlinked modifier genes, epigenetic changes or environmental factors. At least in some cases, complete penetrance appears to require the presence of one or more genetic variants at other loci. In this review, we summarize the evidence for reduced penetrance being a widespread phenomenon in human genetics and explore some of the molecular mechanisms that may help to explain this enigmatic characteristic of human inherited disease.

/pdf/where-genotype-is-not-predictive-of-phenotype-towards-an-4a9ovpgsrt.pdf

Where genotype is not predictive of phenotype: towards an understanding of the molecular basis of reduced penetrance in human inherited disease

Inherited thrombophilia is a blood coagulation disorder that increases the risk for venous thromboembolism (VTE). During the last decades, the practice of testing has evolved from testing selected populations, leading to high perceived risks, to broad testing for various conditions that included VTE, arterial thrombosis, and pregnancy complications. Because results of such tests usually do not guide treatment decisions, not testing patients with VTE for inherited thrombophilia is on the "Choosing Wisely" list endorsed by multiple specialty societies, including ASH. Inherited thrombophilia can be regarded a double-edged sword, as despite the rationale not to test, it is still being performed frequently. Another way of seeing inherited thrombophilia as a double-edged sword lies in its 2-sided association with reproduction, both in men and in women. Current areas of research are whether women with inherited thrombophilia and pregnancy complications benefit from anticoagulant therapy with regard to improving the chance of a successful pregnancy. Potential effects of inherited thrombophilia, most notably factor V Leiden, on improved embryo implantation in women and sperm counts in men are intriguing, but are currently poorly understood.

/pdf/inherited-thrombophilia-a-double-edged-sword-4nekkcvyea.pdf

Inherited thrombophilia: a double-edged sword

Many preanalytical variables may affect the results of routine coagulation assays While advances in laboratory instrumentation have partially addressed the laboratory's ability to recognize some of these variables, there remains an increased reliance on laboratory personnel to recognize the three potential areas where coagulation testing preanalytical issues may arise: (1) specimen collection (including patient selection), (2) specimen transportation and stability, and (3) specimen processing and storage The purpose of this article is to identify the preanalytical variables associated with coagulation-related testing and provide laboratory practice recommendations in an effort to improve the quality of coagulation testing and accuracy of result reporting

/pdf/preanalytical-variables-in-coagulation-testing-setting-the-398z4h4oaq.pdf

Preanalytical Variables in Coagulation Testing: Setting the Stage for Accurate Results.

Pregnancy is a complicated physiological process that might lead to negative outcomes and could threaten the women`s life or the fetus. Miscarriage is a common occurrence in the life cycle of the woman. Exactly how common this experience is not known exactly. Current literature suggests that the cause of RM is only identifiable in up to 40%-50% of cases. Improvement of pregnancy outcome is considered as an important area of action for those concerned with the improvement of womens health and pregnancy outcome. Exploring the relation between blood coagulation mutations with recurrent miscarriages is a challenge. This is due to the fact that recurrent miscarriages are with multiple etiologies, where genetic factors are considered one of those etiologies. Advances technology in molecular genetics provides an accurate and reliable tool to precisely study the genetic abnormalities associated with many diseases. Several studies identified inherited blood coagulation disorders as the principal cause of recurrent miscarriage syndrome. In this review we briefly address the role of inherited blood coagulation disorders in pregnancy and conclude that patients with recurrent miscarriage should be evaluated for clotting disorders, even in the absence of clinical signs because there were some studies concluded that many positive hemophilic causatives finding without any clinical signs .This evaluation may be useful in the Improvement of gynecological care of women with recurrent pregnancy loss and accurate knowledge of all significant complications in these women regarding coagulation disorders and formulate a plan to diagnosis and treatment of these conditions.

The role of Inherited Blood Coagulation Disorders in Recurrent Miscarriage Syndrome

https://onlinelibrary.wiley.com/doi/pdf/10.1111/jth.12876

Survival advantage of heterozygous factor V Leiden carriers in murine sepsis

Factor V Leiden is a procoagulant mutation associated with venous and arterial thrombosis and pregnancy complications. Its high prevalence of 5% in Caucasians suggests that there are evolutionary benefits as well. Carriers are indeed reported to have various advantageous phenotypes related to haemostasis, inflammation and fertility: less acute blood loss; less menstrual blood loss; decreased risk of intracranial haemorrhage; milder phenotypes of haemophilia; higher survival in and lower susceptibility to severe sepsis; higher survival in acute respiratory distress syndrome; less severe diabetic nephropathy and higher fecundity in both men and women. Not all these associations come from high quality adequately powered studies and many have not been confirmed by further research. The evolutionary influence of the alleged associations varies and is difficult to establish, partly due to a shift over time in risk factors of the diseases concerned. For most of the phenotypes possible mechanistic explanations can be provided. The procoagulant phenotype and perhaps also certain pregnancy complications follow from activated protein C (APC) resistance. Elevated APC levels possibly mediate anti-inflammatory effects. Higher sperm counts and more successful embryo implantation seem to play a role in the increased fecundity.

Evolution of Factor V Leiden.

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

M. Levi

Author Tools

Chat about Author

Papers

Evolution of Factor V Leiden.