scholarly journals Cytogenetic signatures of recurrent pregnancy losses

2020 ◽  
Author(s):  
Svetlana. A. Yatsenko ◽  
Cristina Quesada-Candela ◽  
Devereux N. Saller ◽  
Stacy Beck ◽  
Ronald Jaffe ◽  
...  
Keyword(s):  
Genomic Instability ◽  
De Novo ◽  
Chromosomal Abnormalities ◽  
Medical Center ◽  
Clinical Care ◽  
Chromosome Analysis ◽  
Autosomal Aneuploidy ◽  
Genetic Abnormalities ◽  
Structural Chromosome ◽  
Recurrent Pregnancy Losses

ABSTRACTObjectivesTo investigate the incidence of chromosomal abnormalities in the products of conception (POC) of patients with spontaneous miscarriages (SM) and with recurrent pregnancy losses (RPL), and to determine biological mechanisms contributing to RPL.DesignRetrospective cohort study.SettingUniversity-affiliated medical center.PatientsDuring a 20-years period, 12,096 POC samples underwent classical chromosome analysis as a part of standard clinical care.InterventionsCytogenetic findings were classified into six categories and compared between the SM and RPL cohorts.Main Outcome MeasuresRPL-specific cytogenetic abnormalities and sex bias in POCs with autosomal aneuploidy.ResultsAnalysis of a large cohort of RPL patients has identified an increased incidence of inherited and de novo structural chromosome abnormalities, recurrent polyploid conceptions, and complex mosaic alterations. These abnormalities are the signature of genomic instability, posing a high risk of genetic abnormalities to offspring independent of maternal age. Predominance of male conceptions in the RPL cohort points toward X-linked etiology and gender-specific intolerance for certain genetic abnormalities.ConclusionsOur study showed several possible genetic etiologies of RPL, including parental structural chromosome rearrangements, predisposition to meiotic nondisjunction and genomic instability in patients with karyotypically abnormal POCs. Loss of karyotypically normal fetuses might be attributed to defects in genes essential for fetal development and survival, as well as aberrations affecting the X chromosome structure or function. Molecular studies of parental and POC genomes will help to identify inherited defects in genes involved in meiotic divisions and DNA repair to confirm our hypotheses, and to discover novel fetal-essential genes.

scholarly journals A microarray-komparatív genomhibridizálás (arrayCGH) praenatalis alkalmazása. Javaslat a hazai bevezetésre

2019 ◽  
Vol 160 (13) ◽  
pp. 484-493
Author(s):  
Zsolt Tidrenczel ◽  
Erika P. Tardy ◽  
Henriett Pikó ◽  
Edina Sarkadi ◽  
Ildikó Böjtös ◽  
...  
Keyword(s):  
Clinical Utility ◽  
Chromosomal Abnormalities ◽  
Prenatal Testing ◽  
Chromosome Analysis ◽  
Molecular Karyotyping ◽  
Chromosomal Microarray ◽  
Comparative Genome Hybridization ◽  
Genetic Abnormalities ◽  
Array Comparative Genome Hybridization ◽  
Copy Number Changes

Abstract: Invasive prenatal testing and conventional G-banding chromosome analysis have been considered to be the gold standard of fetal cytogenetic diagnosis. Standard karyotyping is, however, constrained by the limits of the resolution of using a microscope. The advantage of molecular karyotyping, array based methods is the evaluation of sub-microscopic copy number changes across the whole genome in a single analysis. The application of array comparative genome hybridization has greatly increased the detection of pathogenic chromosomal abnormalities in prenatal settings. Based on available data in the international literature of the last decade, the clinical utility of arrayCGH is the recognition of some 1–2% and 5–7% additional genetical information compared to metaphase karyotype alone in fetuses without ultrasound anomaly and in fetuses with ultrasonographically detected malformations, respectively. Thus arrayCGH improves the prenatal diagnosis of genetic abnormalities mainly in fetuses with structural sonographic findings. In the present paper we review the literature of chromosomal microarray and make a proposal for the application of the method in Hungarian prenatal genetical practice. Orv Hetil. 2019; 160(13): 484–493.

scholarly journals The genetic abnormalities investigation of leukemia in past few decades

2021 ◽  
Vol 3 (4) ◽  
pp. 01-07
Author(s):  
Ahmad Rahnemoon
Keyword(s):  
Genetic Basis ◽  
Chromosomal Abnormalities ◽  
Molecular Level ◽  
Clonal Evolution ◽  
Chromosome Analysis ◽  
Clonal Proliferation ◽  
Myeloid Progenitor ◽  
Advanced Phase ◽  
Genetic Abnormalities ◽  
Myeloid Progenitor Cells

Cytogenetic and molecular analysis of each patient’s leukemia cells has become an essential component of diagnosis prior to treatment. It has furthered our understanding of leukemogenesis at a molecular level. Specific and well-characterized recurring chromosomal abnormalities facilitate diagnosis, confirm subtype classification, and have major prognostic value for treatment planning. Conventional chromosome analysis is a basic way for diagnosis and treatment. In addition in this way evaluation of disease progression is important and so it is the only method that can identify the presence of clonal evolution, particularly in accelerated and relapse phase in the disease. Also conventional cytogenetic can detect chromosomal abnormality associated with its advanced phase. Anyhow, the value of translocation rates in interphase and metaphase nuclei in monitoring leukemia is at the time of diagnosis and after treatment additionally. Genomic profiling transformed our understanding of the genetic basis of leukemia particularly in acute leukemia, which is a malignant clonal proliferation in lymphoid stem cells or myeloid progenitor cells.

scholarly journals Characterization of a Rare Mosaic Unbalanced Translocation of t(3;12) in a Patient With Neurodevelopmental Disorders

2021 ◽  
Author(s):  
Xiaolin Hu ◽  
Elizabeth K Baker ◽  
Jodie Johnson ◽  
Stephanie Balow ◽  
Loren D.M. Pena ◽  
...  
Keyword(s):  
De Novo ◽  
Chromosomal Abnormalities ◽  
Snp Array ◽  
Chromosome Analysis ◽  
Chromosome 12 ◽  
Derivative Chromosome ◽  
Unbalanced Translocation ◽  
Balanced Translocation ◽  
Chromosomal Disorders ◽  
History Of

Abstract Background Unbalanced translocations may be de novo or inherited from one parent carrying the balanced form and are usually present in all cells. Mosaic unbalanced translocations are extremely rare with a highly variable phenotype depending on the tissue distribution and level of mosaicism. Mosaicism for structural chromosomal abnormalities is clinically challenging for diagnosis and counseling due to the limitation of technical platforms and complex mechanisms, respectively. Here we report a case with a tremendously rare maternally-derived mosaic unbalanced translocation of t(3;12), and we illustrate the unreported complicated mechanism using single nucleotide polymorphism (SNP) array, fluorescence in situ hybridization (FISH), and chromosome analyses. Case Presentation: An 18-year-old female with a history of microcephaly, pervasive developmental disorder, intellectual disability, sensory integration disorder, gastroparesis, and hypotonia presented to our genetics clinic. She had negative karyotype by parental report but no other genetic testing performed previously. SNP microarray analysis revealed a complex genotype including 8.4 Mb terminal mosaic duplication on chromosome 3 (3p26.3->3p26.1) with the distal 5.7 Mb involving two parental haplotypes and the proximal 2.7 Mb involving three parental haplotypes, and a 6.1 Mb terminal mosaic deletion on chromosome 12 (12p13.33->12p13.31) with no evidence for a second haplotype. Adjacent to the mosaic deletion is an interstitial mosaic copy-neutral region of homozygosity (1.9 Mb, 12p13.31). The mother of this individual was confirmed by chromosome analysis and FISH that she carries a balanced translocation, t(3;12)(p26.1;p13.31). Conclusion Taken together, the proband, when at the stage of a zygote, likely carried the derivative chromosome 12 from this translocation, and a postzygotic mitotic recombination event occurred between the normal paternal chromosome 12 and maternal derivative chromosome 12 to “correct” the partial 3p trisomy and partial deletion of 12p. To the best of our knowledge, it is the first time that a mechanism utilizing a combined cytogenetic and cytogenomic approach, and we believe it expands our knowledge of mosaic structural chromosomal disorders and provides new insight into clinical management and genetic counseling.

scholarly journals Risk factors associated with physician trainee concern over missed educational opportunities during the COVID-19 pandemic

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sunny S. Lou ◽  
Charles W. Goss ◽  
Bradley A. Evanoff ◽  
Jennifer G. Duncan ◽  
Thomas Kannampallil
Keyword(s):  
Risk Factors ◽  
Clinical Education ◽  
Medical Center ◽  
Clinical Care ◽  
Academic Medical Center ◽  
Clinical Work ◽  
Educational Opportunities ◽  
Missed Opportunities ◽  
Physician Trainee ◽  
At Home

Abstract Background The COVID-19 pandemic resulted in a transformation of clinical care practices to protect both patients and providers. These changes led to a decrease in patient volume, impacting physician trainee education due to lost clinical and didactic opportunities. We measured the prevalence of trainee concern over missed educational opportunities and investigated the risk factors leading to such concerns. Methods All residents and fellows at a large academic medical center were invited to participate in a web-based survey in May of 2020. Participants responded to questions regarding demographic characteristics, specialty, primary assigned responsibility during the previous 2 weeks (clinical, education, or research), perceived concern over missed educational opportunities, and burnout. Multivariable logistic regression was used to assess the relationship between missed educational opportunities and the measured variables. Results 22% (301 of 1375) of the trainees completed the survey. 47% of the participants were concerned about missed educational opportunities. Trainees assigned to education at home had 2.85 [95%CI 1.33–6.45] greater odds of being concerned over missed educational opportunities as compared with trainees performing clinical work. Trainees performing research were not similarly affected [aOR = 0.96, 95%CI (0.47–1.93)]. Trainees in pathology or radiology had 2.51 [95%CI 1.16–5.68] greater odds of concern for missed educational opportunities as compared with medicine. Trainees with greater concern over missed opportunities were more likely to be experiencing burnout (p = 0.038). Conclusions Trainees in radiology or pathology and those assigned to education at home were more likely to be concerned about their missed educational opportunities. Residency programs should consider providing trainees with research or at home clinical opportunities as an alternative to self-study should future need for reduced clinical hours arise.

scholarly journals Cohort profile of Acutelines: a large data/biobank of acute and emergency medicine

BMJ Open ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. e047349
Author(s):  
Ewoud ter Avest ◽  
Barbara C van Munster ◽  
Raymond J van Wijk ◽  
Sanne Tent ◽  
Sanne Ter Horst ◽  
...  
Keyword(s):  
Acute Care ◽  
De Novo ◽  
Medical Center ◽  
Large Data ◽  
Future Research ◽  
Imaging Data ◽  
Novel Studies ◽  
Long Term Follow Up ◽  
Registration Number

PurposeResearch in acute care faces many challenges, including enrolment challenges, legal limitations in data sharing, limited funding and lack of singular ownership of the domain of acute care. To overcome these challenges, the Center of Acute Care of the University Medical Center Groningen in the Netherlands, has established a de novo data, image and biobank named ‘Acutelines’.ParticipantsClinical data, imaging data and biomaterials (ie, blood, urine, faeces, hair) are collected from patients presenting to the emergency department (ED) with a broad range of acute disease presentations. A deferred consent procedure (by proxy) is in place to allow collecting data and biomaterials prior to obtaining written consent. The digital infrastructure used ensures automated capturing of all bed-side monitoring data (ie, vital parameters, electrophysiological waveforms) and securely importing data from other sources, such as the electronic health records of the hospital, ambulance and general practitioner, municipal registration and pharmacy. Data are collected from all included participants during the first 72 hours of their hospitalisation, while follow-up data are collected at 3 months, 1 year, 2 years and 5 years after their ED visit.Findings to dateEnrolment of the first participant occurred on 1 September 2020. During the first month, 653 participants were screened for eligibility, of which 180 were approached as potential participants. In total, 151 (84%) provided consent for participation of which 89 participants fulfilled criteria for collection of biomaterials.Future plansThe main aim of Acutelines is to facilitate research in acute medicine by providing the framework for novel studies and issuing data, images and biomaterials for future research. The protocol will be extended by connecting with central registries to obtain long-term follow-up data, for which we already request permission from the participant.Trial registration numberNCT04615065.

scholarly journals A Bibliometric Insight of Genetic Factors in ASD: Emerging Trends and New Developments

2020 ◽  
Vol 11 (1) ◽  
pp. 33
Author(s):  
Kang Wang ◽  
Weicheng Duan ◽  
Yijie Duan ◽  
Yuxin Yu ◽  
Xiuyi Chen ◽  
...  
Keyword(s):  
Genetic Factors ◽  
De Novo ◽  
Rapid Development ◽  
The United States ◽  
Research Area ◽  
Scientific Output ◽  
Autism Spectrum ◽  
De Novo Mutations ◽  
Emerging Trends ◽  
Genetic Abnormalities

Autism spectrum disorder (ASD) cases have increased rapidly in recent decades, which is associated with various genetic abnormalities. To provide a better understanding of the genetic factors in ASD, we assessed the global scientific output of the related studies. A total of 2944 studies published between 1997 and 2018 were included by systematic retrieval from the Web of Science (WoS) database, whose scientific landscapes were drawn and the tendencies and research frontiers were explored through bibliometric methods. The United States has been acting as a leading explorer of the field worldwide in recent years. The rapid development of high-throughput technologies and bioinformatics transferred the research method from the traditional classic method to a big data-based pipeline. As a consequence, the focused research area and tendency were also changed, as the contribution of de novo mutations in ASD has been a research hotspot in the past several years and probably will remain one into the near future, which is consistent with the current opinions of the major etiology of ASD. Therefore, more attention and financial support should be paid to the deciphering of the de novo mutations in ASD. Meanwhile, the effective cooperation of multi-research centers and scientists in different fields should be advocated in the next step of scientific research undertaken.

scholarly journals Coping with COVID-19: medical students as strong and responsible stewards of their education

2021 ◽  
Author(s):  
Jacquelyn B. Kercheval ◽  
Deena Khamees ◽  
Charles A. Keilin ◽  
Netana H. Markovitz ◽  
Eve D. Losman
Keyword(s):  
Medical Students ◽  
Curriculum Development ◽  
De Novo ◽  
Traditional Approach ◽  
Clinical Care ◽  
Successful Implementation ◽  
Discussion Boards ◽  
Multiple Choice Questions ◽  
Continued Learning ◽  
Comprehensive Curriculum

Abstract Background Due to the COVID-19 pandemic, clinical rotations at the University of Michigan Medical School (UMMS) were suspended on March 17, 2020, per the Association of American Medical Colleges’ recommendations. No alternative curriculum existed to fill the educational void for clinical students. The traditional approach to curriculum development was not feasible during the pandemic as faculty were redeployed to clinical care, and the immediate need for continued learning necessitated a new model. Approach One student developed an outline for an online course on pandemics based on peer-to-peer conversations regarding learners’ interests and needs, and she proposed that students author the content given the immediate need for a curriculum. Fifteen student volunteers developed content to fill knowledge gaps, and expert faculty reviewers confirmed that the student authors had successfully curated a comprehensive curriculum. Evaluation The crowdsourced student content coalesced into a 40-hour curriculum required for all 371 clinical-level students at UMMS. This student-driven effort took just 17 days from outline to implementation, and the final product is a full course comprising five modules, multiple choice questions, discussion boards, and assignments. Learners were surveyed to gauge success, and 93% rated this content as relevant to all medical students. Reflection The successful implementation of this model for curriculum development, grounded in the Master Adaptive Learner framework, suggests that medical students can be entrusted as stewards of their own education. As we return to a post-pandemic “normal,” this approach could be applied to the maintenance and de novo development of future curricula.

scholarly journals De novo adult acute myeloid leukemia with two new mutations in juxtatransmembrane domain of the FLT3 gene: a case report

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Ismael F. Alarbeed ◽  
Abdulsamad Wafa ◽  
Faten Moassass ◽  
Bassel Al-Halabi ◽  
Walid Al-Achkar ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Chromosomal Abnormalities ◽  
Molecular Genetic ◽  
Type A ◽  
Chemotherapeutic Treatment ◽  
Acute Myeloid ◽  
New Mutations

Abstract Background Approximately 30% of adult acute myeloid leukemia (AML) acquire within fms-like tyrosine kinase 3 gene (FLT3) internal tandem duplications (FLT3/ITDs) in their juxtamembrane domain (JMD). FLT3/ITDs range in size from three to hundreds of nucleotides, and confer an adverse prognosis. Studies on a possible relationship between of FLT3/ITDs length and clinical outcomes in those AML patients were inconclusive, yet. Case presentation Here we report a 54-year-old Arab male diagnosed with AML who had two FLT3-ITD mutations in addition to NPM1 mutation. Cytogenetic approaches (banding cytogenetics) and fluorescence in situ hybridization (FISH) using specific probes to detect translocations t(8;21), t(15;17), t(16;16), t(12;21), and deletion del(13q)) were applied to exclude chromosomal abnormalities. Molecular genetic approaches (polymerase chain reaction (PCR) and the Sanger sequencing) identified a yet unreported combination of two new mutations in FLT3-ITDs. The first mutation induced a frameshift in JMD, and the second led to a homozygous substitution of c.1836T>A (p.F612L) also in JMD. Additionally a NPM1 type A mutation was detected. The first chemotherapeutic treatment was successful, but 1 month after the initial diagnosis, the patient experienced a relapse and unfortunately died. Conclusions To the best of our knowledge, a combination of two FLT3-ITD mutations in JMD together with an NPM1 type A mutation were not previously reported in adult AML. Further studies are necessary to prove or rule out whether the size of these FLT3-ITDs mutations and potential other double mutations in FLT3-ITD are correlated with the observed adverse outcome.

Intrafamilial Variability of the R694C Variant in BICD2 Presenting with Lethal Severe Arthrogryposis

2022 ◽  
pp. 097321792110688
Author(s):  
Francisco Ribeiro-Mourão ◽  
Ana Vilan ◽  
Sara Passos-Silva ◽  
Fernando Silveira ◽  
Miguel Leão ◽  
...  
Keyword(s):  
De Novo ◽  
Bone Fractures ◽  
Muscular Atrophy ◽  
Hip Dislocation ◽  
Arthrogryposis Multiplex Congenita ◽  
Pathogenic Variants ◽  
Genetic Abnormalities ◽  
Heterozygous Variant ◽  
Fetal Movements ◽  
Intrafamilial Variability

Arthrogryposis multiplex congenita (AMC) is a heterogeneous condition comprising congenital multiple joint contractures, and it is secondary to decreased fetal mobility following environmental/genetic abnormalities. BICD2 pathogenic variants have been associated with autosomal dominant spinal muscular atrophy with lower extremity predominance (SMALED2). We report the case of a newborn with decreased fetal movements and ventriculomegaly diagnosed in utero, born with severe AMC, multiple bone fractures, congenital hip dislocation, and respiratory insufficiency that led to neonatal death. His mother had AMC diagnosis without established etiology. Her phenotype characterization was key to guide the genetic investigation. A BICD 2 heterozygous variant (NM_001003800.1; c.2080C > T; p. [Arg694Cys]) was detected both in the mother and the newborn. This variant had previously been reported in 3 cases, all having de novo severe SMALED-type 2B (MIM#618291) phenotype. This is the first report of this variant (p. [Arg694Cys]) presenting with an inherited, severe, and lethal phenotype associated to intrafamilial variability, suggesting a more complex phenotype-genotype correlation than previously stated.

Measurement of Individual Clinical Productivity in an Academic Anesthesiology Department

2000 ◽  
Vol 93 (6) ◽  
pp. 1509-1516 ◽  
Author(s):  
Amr E. Abouleish ◽  
Mark H. Zornow ◽  
Ronald S. Levy ◽  
James Abate ◽  
Donald S. Prough
Keyword(s):  
Medical Center ◽  
Clinical Care ◽  
Obstetric Anesthesia ◽  
Fiscal Year ◽  
Full Time ◽  
Full Time Equivalent ◽  
High Productivity ◽  
Academic Settings ◽  
Individual Productivity ◽  
American Society

Background The ability to measure productivity, work performed, or contributions toward the clinical mission has become an important issue facing anesthesiology departments in private practice and academic settings. Unfortunately, the practice and billing of anesthesia services makes it difficult to quantify individual productivity. This study examines the following methods of measuring individual productivity: normalized clinical days per year (nCD/yr); time units per operating-room day worked (TU/OR day); normalized time units per year (nTU/yr); total American Society of Anesthesiologists (ASA) units per OR day (tASA/OR day); and normalized total ASA units per year (ntASA/yr). Methods Billing and scheduling data for clinical activities of faculty members of an anesthesiology department at a university medical center were collected and analyzed for the 1998 fiscal year. All clinical sites and all clinical faculty anesthesiologists were included unless they spent less than 20% of their time during the fiscal year providing clinical care, i.e., less than 0.2 clinical full-time equivalent. Outliers, defined as faculty who had productivity greater or less than 1 SD from the mean, were examined in detail. Results Mean and median values were reported for each measurement, and different groups of outliers were identified. nCD/yr identified faculty who worked more than their clinical full-time equivalent would have predicted. TU/OR day and tASA/OR day identified apparently low-productivity faculty as those who worked a large portion of their time in obstetric anesthesia or an ambulatory surgicenter. tASA/OR day identified specialty anesthesiologists as apparently high-productivity faculty. nTU/yr and ntASA/yr were products of the per-OR day measurement and nCD/yr. Conclusion Each of the measurements studied values certain types of productivity more than others. By defining what type of service is most important to reward, the most appropriate measure or combination of measures of productivity can be chosen. In the authors' department, nCD/yr is the most useful measure of individual productivity because it measures an individual anesthesiologist's contribution to daily staffing, includes all clinical sites, is independent of nonanesthesia factors, and is easy to collect and determine.

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