Era Of Genetics Research Articles

Growth factors, gene activation and cell recruitment: From intraovarian condensed platelet cytokines to de novo oocyte development

Interest in decelerating or reversing reproductive aging is unlikely to diminish in the era of molecular genetics. For the adult human ovary, meeting the challenge of menopause without synthetic hormone replacement has now moved beyond proof-of-concept, as shown from treatments validated with standard metabolic markers and ovarian reserve estimates. However, without proper recruitment and differentiation of oocytes, such outcomes would be impossible. The full inventory of factors required for such folliculogenesis is not yet final, but growth differentiation factor-9, transforming growth factor-beta1, vascular endothelial growth factor, and insulin-like growth factor-1 are consistently identified as relevant. Platelet-derived growth factor and, more recently, bone morphogenic proteins are also central to cell migration, vascular support, and general ovarian function. Interestingly, when cells secreting these moieties are surgically grafted near undifferentiated oocyte stem precursors, the latency phase transitions to delineate follicle development and restoration of reproductive capacity. Direct intraovarian injection of condensed platelet-derived cytokines (a platelet-rich plasma/PRP product) likewise enables return of menses, ovulation, and term live birth. This report extends our previous work on the proangiogenic effects of intraovarian PRP by connecting clinical responses to specific cytokine-dependent gene activation pathways likely needed to induce oocyte differentiation. Ovarian rejuvenation is a promising new application for platelet-rich plasma and/or condensed plasma cytokines of platelet origin, which are injected into older ovarian tissue.

Regeneration in the phylogenetic empire: an interview with Peter Currie.

Regeneration in the phylogenetic empire: an interview with Peter Currie.

What Is the Weight of a Single Amoeba and Why Does It Matter?

Cell size is an important variable in the study of cellular growth, metabolism, and the cell cycle. The large size of Amoeba proteus and the ease with which it can be collected and cultured have made it a star in biology education—and it was a model for research on cell biology before the introduction of molecular genetic methods. Measuring the cytoplasmic density of a single amoeba without modern instrumentation seems like a difficult task, but this was done with supreme accuracy in the 1940s. The solution was based on the familiar Cartesian diver that is used to demonstrate Archimedes’s principle. It required the fabrication of a tiny diver that would respond to the additional mass of a cell. Experiments using this method allowed investigators to study changes in size and density associated with feeding, starvation, and cell division. This research is an illustration of the ingenuity of cell biologists in the pre-molecular genetic era of their field, which is often overlooked by contemporary scientists. The consideration of the mass, density, and buoyancy of free-living amoebas encourages a new hypothesis about the evolution of testate amoebas.

Guest Editor's Memo: Genetics Moves To Center Stage

Our understanding of pulmonary hypertension (PH) has advanced steadily. Almost 100 years ago, light microscopy provided the earliest insights into a rare progressive and fatal disease, primary pulmonary hypertension (“PPH”). Pathologists described the histopathology of PPH, with terms like “plexogenic” and “microthromboembolic” PPH. Pathologists, who specialized in pulmonary vascular disease, identified two rare disorders, pulmonary veno-occlusive disease (PVOD) and pulmonary capillary hemangiomatosis (PCH), that mimicked PPH clinically, but were distinctly different under the microscope.By the middle of the 20th century, the introduction of pulmonary artery catheterization to the study of cardiovascular diseases produced a new level of understanding of PH based upon physiologic observations of intravascular pressures and flows, with an emphasis on mechanisms that caused constriction and relaxation of pulmonary arterioles. This era supported early efforts to treat sporadic PPH and familial PPH, now known as idiopathic and heritable pulmonary arterial hypertension (PAH) with vasodilators, eventually leading to treatments which targeted three pathways integral to vasoconstriction and vasodilation of pulmonary arterioles.Even as pathologic, physiologic, and treatment studies proceeded during the second half of the 20th century, the genetic era began. Investigators took advantage of scientific advances in genetics to discover heritable causes of PH. The first breakthrough occurred in 2000, when two research teams independently reported that mutations in the gene (BMPR2), encoding the bone morphogenetic protein type 2 receptor, caused familial PPH. Over the next two decades investigators linked DNA sequence variations in 16 additional genes to heritable forms of PAH, including PVOD and PCH. These discoveries shaped a new understanding of PAH.Investigators quickly determined that BMPR2 regulated the proliferation of vascular cells, not vasoconstriction. Recognition of the pivotal role of cellular proliferation and transforming growth factor β (TGF-β) signaling paved the way for a new approach to the treatment of PAH. In the Study of Sotatercept for the Treatment of Pulmonary Arterial Hypertension (PULSAR), sotatercept, a fusion protein that impairs activation of a TGFβ pro-proliferative pathway, produced a greater reduction in pulmonary vascular resistance than placebo. Now studies are underway to assess the efficacy and safety of sotatercept across a broad spectrum of PAH disease severity.We have entered a new era of understanding and treating PAH, as genetics moves to center stage. This issue of Advances in Pulmonary Hypertension was organized to serve as a valuable resource for the PH community. The first article, authored by Drs. Carrie Welch and Wendy Chung of Columbia University, provides a comprehensive overview of the genomics of pulmonary hypertension. With this foundation in place, the second article, authored by Rachel Sullivan, MD (Stanford University) and Eric Austin, MD (Vanderbilt University) reviews the relationships between specific gene sequence variations and PAH phenotypes that clinicians are likely to encounter.In recent years genetic counseling and genetic testing have become important affordable services for patients with PAH and their families. Sumathi Rachamadugu, MSc, MS and Melanie Emmerson, MS (Intermountain Healthcare) collaborated with Barbara Girerd, PhD (Université Paris-Saclay) and Hunter Best, PhD (University of Utah) to provide an in depth introduction pretest genetic counseling, genetic testing, and posttest genetic counseling for PAH patients and their families. The PH Professional network contribution by Athena Angelopoulos, MS and Rachel Farrell, MS (University of California San Francisco) complements the preceding article by providing additional details related to genetic counseling and testing for PAH patients and their families.Finally, Drs. Austin, Chung, and Yu, joined us for a roundtable discussion on the genetics of pulmonary hypertension. Participants shared their personal knowledge of the history of genetic research and discovery related to PH, their advice on discussing genetic aspects of PH with patients and families, their thoughts about involving genetic counselors and ordering genetic tests, as well as how genetic test results influence treatment decisions and how knowledge of molecular pathways informs the development of new medications to treat PAH.In closing, we thank the authors and everyone at PHA and Allen Press who worked so hard to produce this issue of Advances.

A historical overview of advances in molecular genetic/genomic studies of the ABO blood group system.

In 1990, 90 years after the discovery of ABO blood groups by Karl Landsteiner, my research team at the Molecular Biology Laboratory of the now-defunct Biomembrane Institute elucidated the molecular genetic basis of the ABO polymorphism. Henrik Clausen, Head of the Immunology Laboratory, initiated the project by isolating human group A transferase (AT), whose partial amino acid sequence was key to its success. Sen-itiroh Hakomori, the Scientific Director, provided all the institutional support. The characterization started from the 3 major alleles (A1, B, and O), and proceeded to the alleles of A2, A3, Ax and B3 subgroups and also to the cis-AB and B(A) alleles, which specify the expression of A and B antigens by single alleles. In addition to the identification of allele-specific single nucleotide polymorphism (SNP) variations, we also experimentally demonstrated their functional significance in glycosyltransferase activity and sugar specificity of the encoded proteins. Other scientists interested in blood group genes later characterized more than 250 ABO alleles. However, recent developments in next-generation sequencing have enabled the sequencing of millions of human genomes, transitioning from the era of genetics to the era of genomics. As a result, numerous SNP variations have been identified in the coding and noncoding regions of the ABO gene, making ABO one of the most studied loci for human polymorphism. As a tribute to Dr. Hakomori's scientific legacy, a historical overview in molecular genetic/genomic studies of the human ABO gene polymorphism is presented, with an emphasis on early discoveries made at his institute.Graphical abstract

The epilepsy-autism spectrum disorder phenotype in the era of molecular genetics and precision therapy.

Autism spectrum disorder (ASD) is frequently associated with infants with epileptic encephalopathy, and early interventions targeting social and cognitive deficits can have positive effects on developmental outcome. However, early diagnosis of ASD among infants with epilepsy is complicated by variability in clinical phenotypes. Commonality in both biological and molecular mechanisms have been suggested between ASD and epilepsy, such as occurs with tuberous sclerosis complex. This review summarizes the current understanding of causal mechanisms between epilepsy and ASD, with a particularly genetic focus. Hypothetical explanations to support the conjugation of the two conditions include abnormalities in synaptic growth, imbalance in neuronal excitation/inhibition, and abnormal synaptic plasticity. Investigation of the probable genetic basis has implemented many genes, although the main risk supports existing hypotheses in that these cluster to abnormalities in ion channels, synaptic function and structure, and transcription regulators, with the mammalian target of rapamycin (mTOR) pathway and "mTORpathies" having been a notable research focus. Experimental models not only have a crucial role in determining gene functions but are also useful instruments for tracing disease trajectory. Precision medicine from gene therapy remains a theoretical possibility, but more contemporary developments continue in molecular tests to aid earlier diagnoses and better therapeutic targeting.

Mapping the Diverse and Inclusive Future of Parkinson's Disease Genetics and Its Widespread Impact.

Over the last decades, genetics has been the engine that has pushed us along on our voyage to understand the etiology of Parkinson’s disease (PD). Although a large number of risk loci and causative mutations for PD have been identified, it is clear that much more needs to be done to solve the missing heritability mystery. Despite remarkable efforts, as a field, we have failed in terms of diversity and inclusivity. The vast majority of genetic studies in PD have focused on individuals of European ancestry, leading to a gap of knowledge on the existing genetic differences across populations and PD as a whole. As we move forward, shedding light on the genetic architecture contributing to PD in non-European populations is essential, and will provide novel insight into the generalized genetic map of the disease. In this review, we discuss how better representation of understudied ancestral groups in PD genetics research requires addressing and resolving all the challenges that hinder the inclusion of these populations. We further provide an overview of PD genetics in the clinics, covering the current challenges and limitations of genetic testing and counseling. Finally, we describe the impact of worldwide collaborative initiatives in the field, shaping the future of the new era of PD genetics as we advance in our understanding of the genetic architecture of PD.

Development of the technologies and cognition of prenatal screening and prenatal diagnosis in an era of molecular genetics

<p indent="0mm">Original prenatal diagnostic testing focused primarily on chromosomal aneuploidies. Advances in genetics and genomic medicine have led to a dramatic increase in the availability of genetic testing, including in the prenatal period. Prenatal diagnosis is available for an ever-increasing number of disorders, including copy number variants, single gene disorders, and uniparental disomy. Prenatal genetic testing has stepped from the cytogenetic era into the molecular era. At the same time, prenatal screening has improved with development of cell-free DNA (cfDNA) screening, as well as expanded carrier screening for a broad array of inherited conditions. The advances in the technologies promote scientific research in this area and have altered people’s cognition of prenatal screening and prenatal diagnosis.

Life Writing in the Era of Genetics: Contemporary Genetic Risk Narratives in Great Britain and America

The development of genetic science brings forth a third group besides the healthy and the ill: the high-risk group who carries certain disease-related genes. In the era of genetics, people try to assess risks with statistical numbers and eliminate risks by Western medical measures. In this context, personal genetic risk narratives (usually in the form of memoirs) emerged in Great Britain and America in the 1990s. The thesis has a close reading of three British and American genetic risk memoirs and wants to find the characteristics and values of the new genre. The memoirs are featured by their vivid description of the narrator&amp;rsquo;s difficult and complex situation in face of genetic risks. In an era when the body is dominated by statistical numbers, these narratives make personal meaning of impersonal statistics. Genetic risk narratives express a strong belief in genetic technology and Western medical myth. However, the narrative divergence and self-contradiction in the memoirs exposes the limitation of genetic determinism and thus deconstructs the Western medical myth.

Moving forward with forward genetics: A summary of the INFRAFRONTIER Forward Genetics Panel Discussion

In the last few decades, forward genetics approaches have been extensively used to identify gene function. Essentially, forward genetics is the elucidation of the genetic basis of a specific phenotype by screening a population containing random genomic modifications that alter gene function. These approaches have shed light on some essential gene functions in development and disease and have expanded the realm of understanding for genetic disorders. Due to the availability of efficient mutagenesis methods, phenotyping techniques, reliable validation, comprehensive sequence information and translational potential, mouse models are favored for forward genetics approaches. However, in this post-genomic CRISPR-Cas9 era, the relevance and future of forward genetics was brought into question. With more than 7300 mouse strains archived and close interactions with several leading mouse researchers around the world, INFRAFRONTIER - the European Research Infrastructure for mouse models organised a panel discussion on forward genetics at the International Mammalian Genome Conference 2018 to discuss the future of forward genetics as well as challenges faced by researchers using this approach in the current research environment. The commentary presents an overview of this discussion.

Moving forward with forward genetics: A summary of the INFRAFRONTIER Forward Genetics Panel Discussion.

In the last few decades, forward genetics approaches have been extensively used to identify gene function. Essentially, forward genetics is the elucidation of the genetic basis of a specific phenotype by screening a population containing random genomic modifications that alter gene function. These approaches have shed light on some essential gene functions in development and disease and have expanded the realm of understanding for genetic disorders. Due to the availability of efficient mutagenesis methods, phenotyping techniques, reliable validation, comprehensive sequence information and translational potential, mouse models are favored for forward genetics approaches. However, in this post-genomic CRISPR-Cas9 era, the relevance and future of forward genetics was brought into question. With more than 7300 mouse strains archived and close interactions with several leading mouse researchers around the world, INFRAFRONTIER - the European Research Infrastructure for mouse models organised a panel discussion on forward genetics at the International Mammalian Genome Conference 2018 to discuss the future of forward genetics as well as challenges faced by researchers using this approach in the current research environment. The commentary presents an overview of this discussion.

Rice Breeding in Vietnam: Retrospects, Challenges and Prospects

Rice breeding was conducted for a long time during historical times and is an important job in Vietnam because rice is the major food for domestic consumption and export. In this review, we have provided a comprehensive insight into the importance of promising rice germplasm resources, breeding achievements, and breeding approaches as well as discussed challenges and perspectives of rice breeding in this country. With rice germplasm and wild rice relative resources with rich and various genetic diversity, their useful genes and traits have been exploited and integrated into commercial varieties as the final outputs of rice breeding programs. New achievements of the modern genetics era have been approached and effectively contributed to breeding activities in this country. Genome sequences, molecular breeding, and mutation are powerful tools and playing vital roles in developing new varieties with characteristics of interest that should be followed by the current market demands. In the last decades, there has been a plethora of newly generated varieties by Vietnamese scientists and rice breeders and approved by the state authorities. However, very few domestic mega varieties have prevailed over the imported varieties. Therefore, rice breeding in this country is faced with big challenges, including limitations of backgrounds, budgets, and even talents in basic research to compete with other rice-producing countries. The target goals and long-term approaches for rice breeding should be paid explicitly in priority to ensure national food security and the advantage and development of rice breeding in this country.

Coronavirus in light of philosophy

The history of humanity is a history of rationality. As a result, mankind has progressed from the Stone Age to the era of modern medicine, genetics, computer science, robotics, and nanotechnology. The life span of a man in ancient times was about twenty years, and today, in highly developed societies, a man lives, on average, to eighty-six years. Advances in science and technology have not always had a positive impact. Suffice to say, the ongoing environmental problems that seriously affect humanity or, for example, the dietary problems that have resulted due to genetic manipulation. Scientific and technological development must be considered in a serious and philosophical manner. Ethics are increasingly becoming an integral part of life. In this paper, we focused on the new coronavirus that has led to the planetary-wide disease called COVID-19. All countries have engaged in their efforts to suppress the resulting pandemic. However, some of the utilized measures have been suspect: whether to lock-down people in quarantine, whether their movement should be restricted, whether they should be forced to vaccinate, and so on. Claiming to act prophylactically, scientists, by adding some DNA, RNA segments (gain of function, GOF) to an innocuous human virus, have created a dangerous artificial influenza virus. Likewise, an artificial, infectious coronavirus was created in a laboratory. Both procedures for creating these dangerous, hybrid viruses have been described in eminent scientific journals. The scientists involved in this research told us that they wanted to find cures and vaccines for these non-natural viruses on the off-chance they ever appeared among humans; when carefully handled, engineered organisms provide a unique opportunity to study biological systems in a controlled fashion. Biotechnology is a powerful tool to advance medical research and should not be abandoned because of irrational fears. But the chance of this type of virus appearing among humans is almost non-existent. However, what if these viruses "escape" from the lab, as has happened in the recent past? What if a terrorist organization start producing these viruses on their own according to detailed instructions and then use them? Finally, since the two great world powers, the US and China, that jointly created the artificial coronavirus, called SHC014-MA15, who can stop them from continuing this practice? Isn't it possible that they also created the current SARS-CoV-2 provoking a death of two and a half million people? Related to these questions, this study deals with the issue of tolerance. A large number of world-renowned scientists really believe that the current cause of the pandemic, SARS-CoV-2, is an artificial, laboratory-created virus, presenting a number of facts for this. It is not disputed that their claims are arguable. This, however, does not mean that their opponents, pharmaceutical companies and some superpowers, who have far greater political and economic power, have to incorrectly and utterly embarrass them all over, morally discredit them, nor ban their texts on the subject. In science, the struggle must be waged by arguments, not by totalitarian Orwellian methods.

Recent Advances in the Application of CRISPR/Cas9 Gene Editing System in Poultry Species.

CRISPR/Cas9 system genome editing is revolutionizing genetics research in a wide spectrum of animal models in the genetic era. Among these animals, is the poultry species. CRISPR technology is the newest and most advanced gene-editing tool that allows researchers to modify and alter gene functions for transcriptional regulation, gene targeting, epigenetic modification, gene therapy, and drug delivery in the animal genome. The applicability of the CRISPR/Cas9 system in gene editing and modification of genomes in the avian species is still emerging. Up to date, substantial progress in using CRISPR/Cas9 technology has been made in only two poultry species (chicken and quail), with chicken taking the lead. There have been major recent advances in the modification of the avian genome through their germ cell lineages. In the poultry industry, breeders and producers can utilize CRISPR-mediated approaches to enhance the many required genetic variations towards the poultry population that are absent in a given poultry flock. Thus, CRISPR allows the benefit of accessing genetic characteristics that cannot otherwise be used for poultry production. Therefore CRISPR/Cas9 becomes a very powerful and robust tool for editing genes that allow for the introduction or regulation of genetic information in poultry genomes. However, the CRISPR/Cas9 technology has several limitations that need to be addressed to enhance its use in the poultry industry. This review evaluates and provides a summary of recent advances in applying CRISPR/Cas9 gene editing technology in poultry research and explores its potential use in advancing poultry breeding and production with a major focus on chicken and quail. This could aid future advancements in the use of CRISPR technology to improve poultry production.

Human Genetic Research in Pakistan: Challenges and Way forward

The 90s ushered in the era of molecular genetics in Pakistan. Our centuries’ old tradition of consanguineous marriages, resulting in the availability of large, inbred families with inherited disorders, proved to be a goldmine for geneticists, working to discover new genes and their functions. A multitude of novel genes with previously unknown functions were discovered through genetic linkage analysis, a technique that compares the segregations of DNA markers in normal and affected family members to pinpoint the region that contains the suspect gene. The first few landmark publications on linkage analysis in genetic diseases, from Pakistan, identified only the regions harboring the suspected disease genes.1,2 As the field advanced, disease causing mutations segregating in affected family members were identified through Sanger DNA sequencing of candidate genes in the linked region. In the last decade, the advent of high throughput techniques such as whole exome analysis and animal disease modeling, functional genomics studies became an integral of part of such genetic studies. In addition, bioinformatics tools were developed for predictive modeling of the effect of mutations on protein structure.&#x0D; The analysis of a single large multigenerational family with a genetic disorder could provide the same information that would be obtained from many small nuclear families, as usually found in developed countries. This allowed Pakistani researchers to attract collaborators from Universities around the world. DNA samples of numerous Pakistani families were sent to labs across the world for analysis, many times accompanied by a PhD student who would typically spend around six months working on those families. Universities developed efficient pipelines, whereby students would find families with genetic diseases, extract DNA and carry out linkage analysis and, in some cases, identify the gene mutations using Sanger sequencing. This led to a significant increase in the number of publications on genetics, from Pakistan. However, despite all the good work carried in the country, no credible effort had been made to build national capacity to carry the work beyond initial mutation screening.&#x0D; We lack the ability to conduct good quality high through put –omics analysis and animal model studies within the country. There are several reasons for this. Firstly, the cost of such research is prohibitive. While some institutes have invested in next generation sequencing platforms, these machines are largely underutilized due to high cost of consumables. Lack of adequate funding for reagents, required for genomic, transcriptomic and proteomic studies, is a major roadblock. Secondly, the ease in attracting foreign collaborators to carry out the functional studies in their labs, has made many Pakistani researchers complacent, often, they are happy to be co-authors in research papers without having to go through the pains to set up the required laboratory facilities. Lastly, the bureaucratic processes and red tape, especially in public sector Universities, make procurement of chemicals and consumables, tedious and time consuming, resulting in demotivation of researchers and faculty. There is a need to address these issues, if we wish to move towards self-sufficiency in conducting high level functional genomics and stem the flow of biological samples from Pakistan. &#x0D; While genetic studies in Pakistan have resulted in the discovery of many novel genes, the benefit of these studies is yet to trickle down to the patients. The willingness of the affected families to participate in these studies is crucial. Many affected families belong to far flung rural areas and have no understanding of their disease, how it is inherited or the implications of participating in such research. It is unlikely that families participating in these studies have any immediate benefits and they should be informed at the time of recruitment using common language which they are able to understand. The role of Institutional Ethics and Review Boards, for the protection of study participants and their rights, needs to be strengthened. It is important not to abandon these families after sample collection but to relay the results of the study and counsel them regarding their future options.&#x0D; Despite the rapid advances in genetic medical knowledge, our population has yet to reap its benefits. A small step in right direction is the Compulsory Blood Test of the Relatives of Thalassemia Patient Bill-2017, which makes it compulsory for couples to get tested before marrying. However, the scarcity of gene testing facilities and healthcare professionals trained in clinical genetics is an impediment to the implementation of this bill in the true spirit. It is becoming imperative to educate our healthcare professionals regarding the application of genetics to medical practice. Clinical genetics and its related competencies need to be recognized as medical specialties in the country, before they can be introduced into mainstream clinical practice to improve health outcomes of our affected families.&#x0D;

The Contribution of Somatic Expansion of the CAG Repeat to Symptomatic Development in Huntington's Disease: A Historical Perspective.

The discovery in the early 1990s of the expansion of unstable simple sequence repeats as the causative mutation for a number of inherited human disorders, including Huntington’s disease (HD), opened up a new era of human genetics and provided explanations for some old problems. In particular, an inverse association between the number of repeats inherited and age at onset, and unprecedented levels of germline instability, biased toward further expansion, provided an explanation for the wide symptomatic variability and anticipation observed in HD and many of these disorders. The repeats were also revealed to be somatically unstable in a process that is expansion-biased, age-dependent and tissue-specific, features that are now increasingly recognised as contributory to the age-dependence, progressive nature and tissue specificity of the symptoms of HD, and at least some related disorders. With much of the data deriving from affected individuals, and model systems, somatic expansions have been revealed to arise in a cell division-independent manner in critical target tissues via a mechanism involving key components of the DNA mismatch repair pathway. These insights have opened new approaches to thinking about how the disease could be treated by suppressing somatic expansion and revealed novel protein targets for intervention. Exciting times lie ahead in turning these insights into novel therapies for HD and related disorders.

Managing Vascular Anomalies in the Era of Genetics and Precision Medicine: An Opportunity or a Challenge?

The era of genetics and precision medicine has been reforming this world. How will plastic surgeons in the field of vascular anomalies conform to the trend? This article systematically reviews the identification of serum biomarkers, risk factors, specific mutations in the angiogenesis-related genes such as GNAQ, RASA1, TEK, and their impact on the diagnosis and treatment of vascular anomalies with preliminary results that have been previously reported and leading the tide. Moreover, a new disease classification for complex vascular malformations based on PIK3CA genetic evidence and various treatment breakthroughs is briefly summarized. With gene sequencing, bioinformatics, and big data, we confront the challenges of research in the vascular anomalies domain and explore possibilities of precision medicine development.

Electrical status epilepticus during slow-wave sleep (ESES): Current perspectives

ABSTRACTElectrical status epilepticus during slow-wave sleep (ESES) is an epilepsy syndrome with sleep-induced epileptic discharges and acquired impairment of cognition or behavior. Since the disease’s original description in 1971, no clear consensus has emerged on diagnostic criteria or optimal treatment. The treatment of ESES can be challenging, often including numerous antiepileptic drugs, immunomodulatory agents, and even surgical interventions. There is little evidence to guide treatment because only retrospective studies and case reports on the efficacy of treatment of ESES are present in literature. In this paper, we aim to analyze the etiopathogenesis of ESES in the new genetic era and to evaluate the treatment modalities in accordance with the genetic data and electroclinic spectrum of ESES.

Pre- and Post-Treatment Imaging of Primary Central Nervous System Tumors in the Molecular and Genetic Era.

Recent advances in the molecular and genetic characterization of central nervous system (CNS) tumors have ushered in a new era of tumor classification, diagnosis, and prognostic assessment. In this emerging and rapidly evolving molecular genetic era, imaging plays a critical role in the preoperative diagnosis and surgical planning, molecular marker prediction, targeted treatment planning, and post-therapy assessment of CNS tumors. This review provides an overview of the current imaging methods relevant to the molecular genetic classification of CNS tumors. Specifically, we focused on 1) the correlates between imaging features and specific molecular genetic markers and 2) the post-therapy imaging used for therapeutic assessment.

Onset features and time to diagnosis in Friedreich\u2019s Ataxia

BackgroundIn rare disorders diagnosis may be delayed due to limited awareness and unspecific presenting symptoms. Herein, we address the issue of diagnostic delay in Friedreich’s Ataxia (FRDA), a genetic disorder usually caused by homozygous GAA-repeat expansions.MethodsSix hundred eleven genetically confirmed FRDA patients were recruited within a multicentric natural history study conducted by the EFACTS (European FRDA Consortium for Translational Studies, ClinicalTrials.gov-Identifier NCT02069509). Age at first symptoms as well as age at first suspicion of FRDA by a physician were collected retrospectively at the baseline visit.ResultsIn 554 of cases (90.7%), disease presented with gait or coordination disturbances. In the others (n = 57, 9.3%), non-neurological features such as scoliosis or cardiomyopathy predated ataxia. Before the discovery of the causal mutation in 1996, median time to diagnosis was 4(IQR = 2–9) years and it improved significantly after the introduction of genetic testing (2(IQR = 1–5) years, p < 0.001). Still, after 1996, time to diagnosis was longer in patients with a) non-neurological presentation (mean 6.7, 95%CI [5.5,7.9] vs 4.5, [4.2,5] years in those with neurological presentation, p = 0.001) as well as in b) patients with late-onset (3(IQR = 1–7) vs 2(IQR = 1–5) years compared to typical onset < 25 years of age, p = 0.03).Age at onset significantly correlated with the length of the shorter GAA repeat (GAA1) in case of neurological onset (r = − 0,6; p < 0,0001), but not in patients with non-neurological presentation (r = − 0,1; p = 0,4). Across 54 siblings’ pairs, differences in age at onset did not correlate with differences in GAA-repeat length (r = − 0,14, p = 0,3).ConclusionsIn the genetic era, presentation with non-neurological features or in the adulthood still leads to a significant diagnostic delay in FRDA. Well-known correlations between GAA1 repeat length and disease milestones are not valid in case of atypical presentations or positive family history.