Medical Genetics Commons^™

The Use Of Prognostic Markers To Predict Disease Progression And Clinical Outcome In Monoclonal Gammopathy Of Undetermined Significance, Smouldering Multiple Myeloma And Multiple Myeloma., Róisín C. Mcmonagle

International Undergraduate Journal of Health Sciences

Multiple Myeloma (MM) is an incurable plasma cell malignancy with a complex and incompletely understood molecular pathogenesis. Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smouldering Multiple Myeloma (SMM) precede MM, with variable risks and rates of disease progression. The continuing high relapse and death rate in MM cases has prompted research into more accurate prognostic markers to predict progression from MGUS and SMM to MM, as well as identify MM cases with aggressive disease, in order to begin early, targeted and effective therapeutic intervention. Many studies have focused on utilising current markers more effectively, including M-protein, serum-free light chain ratio, …

Association Between Rs2787094 Genetic Variants In Adam33 Gene And Asthma In Indonesian Population: Preliminary Study, Kencono Viyati, Kinasih Prayuni, Yenni Zulhamidah, Intan Razari, Rika Yuliwulandari

Makara Journal of Health Research

Background: Asthma is a multifactorial disease that encompasses a multitude of genetic and environmental factors. One such factor is the disintegrin and metalloprotein-33 (ADAM33) gene, which is correlated with asthma and bronchial hyperresponsiveness. Previous studies conducted on Asian populations have reported a significant association between rs2787094 polymorphism in the ADAM33 gene and asthma.

Methods: Our study involved 153 Indonesian participants. TaqMan genotyping assay was used to analyze rs2787094 polymorphism in the ADAM33 gene.

Results: No significant association was detected between the allele and genotype frequencies of rs2787094 and asthma in the case and control subjects (p …

Extrinsic Allergic Alveolitis: A Systematic Review Of Hla-Dr In Pigeon Breeder’S Disease, Dylan Thibaut, Ryan A. Witcher, Anitha Kunnath, James Toldi

Advances in Clinical Medical Research and Healthcare Delivery

Abstract

Introduction: Pigeon Breeder’s Pneumonitis (PBP) results due to a complex pathophysiology that includes exposure to avian antigens. Susceptibility has been linked to human leukocyte antigen (HLA) class II, though consensus has not been reached. The goal of this systematic review is to further elucidate the association between PBP and HLA-DR subtypes.

Methods: Databases utilized included PubMed, Google Scholar, ScienceDirect, and Cochrane Library. Inclusion required a minimum of three studies in English presenting HLA-DR alleles of PBP and control subgroups. Exclusion was due to insufficient data or non-feasible control groups. Forest plots were created for HLA-DR subtypes’ association …

Determinism V. Free Will & Genetic Evidence Of Addiction In Plea Bargaining And Sentence Mitigation: Conversion Of Incarceration To Probation And Rehabilitation Based On Genetic Addiction Risk Severity (Gars) Test, Kenneth Blum, Paul Mullen, Richard Green

St. Mary's Law Journal

In this Article, Dr. Kenneth Blum and his team present the case of a presently abstinent, thirty-five year old alcoholic (“AG”) who has several convictions for DWI. AG has undergone and continues to be engaged in out-patient substance abuse treatment. He entered treatment before adjudication and was mandated by the court to continue treatment to assist in maintaining sobriety. Treatment included the administration of the Genetic Addiction Risk Severity (“GARS”) Test.

AG was facing a probable five-year sentence for his fifth DWI conviction in Bexar County, Texas. However, because AG’s genetic risk results indicated a genetically induced dopamine dysfunction, hypodopaminergia, …

Should Health Systems Share Genetic Findings With At-Risk Relatives When The Proband Is Deceased? Interviews With Individuals Diagnosed With Lynch Syndrome, Jessica Ezzell Hunter, Jennifer L. Schneider, Alison J. Firemark, James V. Davis, Sara Gille, Pamala A. Pawloski, Su-Ying Liang, Victoria Schlieder, Alanna Kulchak Rahm

Journal of Patient-Centered Research and Reviews

Purpose: Genetic information has health implications for patients and their biological relatives. Death of a patient before sharing a genetic diagnosis with at-risk relatives is a missed opportunity to provide important information that could guide interventions to minimize cancer-related morbidity and mortality in relatives.

Methods: We performed semi-structured interviews with individuals diagnosed with Lynch syndrome at 1 of 4 health systems to explore their perspectives on whether health systems should share genetic risk information with relatives following a patient’s death. An inductive, open-coding approach was used to analyze audio-recorded content, with software-generated code reports undergoing iterative comparative analysis by a …

Association Of Methylenetetrahydrofolate Reductase Rs1801133 Genetic Variants With Type 2 Diabetes Mellitus And Diabetic Nephropathy, Aysegul Bayramoglu, Gokhan Bayramoglu, Halil Ibrahım Guler, Nezaket Coban, Mustafa Çagatay Korkmaz

Makara Journal of Health Research

Background: Type 2 diabetes mellitus (T2DM) is a complex metabolic disease with a genetic predisposition. Methylenetetrahydrofolatereductase (MTHFR) gene is one of the candidate genes associated with T2DM and diabetic nephropathy (DN). This research was carried out to determine the frequency of the C677T polymorphism (rs1801133) of the MTHFR gene and examine the role of rs1801133 polymorphism in T2DM and DN development.

Methods: DNA was obtained from peripheral blood samples (273 samples) using a DNA isolation kit. MTHFR rs1801133 polymorphism was determined using polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP), and electrophoresis. PCR products were cut by …

Differential Microrna Expression In Glioblastoma As A Therapeutic Target Or Potential Biomarker, Drew Hines, Levi Marcum, Aubrey Strong, Ryan Wade

Channels: Where Disciplines Meet

MicroRNA (miRNA) is an epigenetic factor that plays an important role in the post-transcriptional regulation of gene and protein expression. Recent research has shown that in many types of cancer, differentially expressed levels of certain types of miRNA are significantly correlated with the transformation of and ongoing issues caused by cancer cells. Specifically, in Glioblastoma, one of the most lethal and aggressive human cancers, differential levels of miRNAs contribute to the cell’s lack of pro-apoptotic gene presence and its high resistance to current treatments. Results from current studies could provide information about which microRNAs are differentially expressed in glioblastoma when …

The Ratio Method: Addressing Complex Tort Liability In The Fourth Industrial Revolution, Harrison C. Margolin, Grant H. Frazier

St. Mary's Law Journal

Emerging technologies of the Fourth Industrial Revolution show fundamental promise for improving productivity and quality of life, though their misuse may also cause significant social disruption. For example, while artificial intelligence will be used to accelerate society’s processes, it may also displace millions of workers and arm cybercriminals with increasingly powerful hacking capabilities. Similarly, human gene editing shows promise for curing numerous diseases, but also raises significant concerns about adverse health consequences related to the corruption of human and pathogenic genomes.

In most instances, only specialists understand the growing intricacies of these novel technologies. As the complexity and speed of …

Integrating Patient-Reported Outcomes Into Clinical Genetic Testing For Familial Hypercholesterolemia, Rachele M. Hendricks-Sturrup, Robert Block, Christine Y. Lu

Journal of Patient-Centered Research and Reviews

Patient-reported outcomes (PROs) and PRO measures (PROMs) are often used to help clinicians and researchers understand patients’ personal concerns, feelings, experiences, and perspectives following the implementation of an intervention. Notably, PROs and PROMs can inform health systems, health policy, and payers on the utility of clinical genetic testing based on each patient’s personal values, perspectives, and potential health behaviors subsequent to testing. In this topic synopsis, we discuss the underexplored role of and implications for PROs and PROMs following genetic testing for familial hypercholesterolemia (FH), an autosomal dominant genetic disorder of cholesterol metabolism that can lead to highly premature fatal …

Collagen-Based Biomaterials With Possible Therapeutic Effects, Ramona Mihaela Nedelcuţă, Gigi Călin, Mihai Cristian Nedelcuţă, Vlad Dumitru Baleanu, Dragos Virgil Davitoiu, Bogdan Socea, Bogdan-Petre Stănoiu

Journal of Mind and Medical Sciences

Epidermolysis bullosa (EB) is a rare, serious genetic disease, incurable through the current means. Apart from this initial definition, there was later some ease in the definition of the disease, including the manifestations of toxic epidermal necrolysis and Stevens Johnson syndrome in this entity. In medical practice, there are cases that do not overlap with the description in the literature, thus the treatment must be adapted and personalized to the particularities. We present the case of a female new-born, with "de novo" mutation for the early-onset antenatal epidermolysis and our personalized therapeutic management, based on collagen from bovine corneas by …

How Opportune Is Multigene Testing In Metastatic Colorectal Cancer? A Review, Cristina Orlov-Slavu, Andreea Parosanu, Mihaela Olaru, Dragos Serban, Ioana Paunica, Cornelia Nitipir

Journal of Mind and Medical Sciences

Personalized treatment in oncology is the most innovative method of care. The best method to establish personalized treatment is by genetic characterization of the malignant cell.

Theoretically, the more detailed the characterization, the more effective the choice of treatment becomes. Currently, there are fast and relatively low-cost options that allow such genetic characterization. However, test results sometimes do not detect targetable alterations and, even if they do detect, the use of the treatment-alteration combination does not always generate a satisfactory oncological response.

The present paper aims to answer two questions. First, how targetable can the most common gene alterations in …

Genetic Testing Reveals Germline Mutations Among Patients Undergoing Surgery For Colorectal Carcinoma In A Community Hospital Setting, Alex R. Jones, Dana Greer Rn, Bsn, Ocn, Karin L. Cole Md

Journal of Maine Medical Center

Introduction: Defined germline mutations contribute to 5% to 10% of cases of colorectal carcinoma (CRC). While protocols for universal tumor screening have been adopted to detect mismatch repair (MMR) protein deficiency, widespread multigene panel testing has not been achieved. Barriers to implementing testing protocols may occur in community settings.

Methods: A total of 160 patients presenting for surgical management of CRC between 2011 and 2020 were considered for retrospective analysis in a single-surgeon, single-institution, community-based cohort. The rate of multigene panel testing and prevalence of germline mutations were calculated, and patient characteristics were assessed.

Results: A total of 32/160 (20%) …

The Influence Of Tas2r38 Bitter Taste Gene Polymorphisms On Obesity Risk In Three Racially Diverse Groups, Chaowanee Chupeerach, Pradtana Tapanee, Nattira On-Nom, Piya Temviriyanukul, Boonrat Chantong, Nicole Reeder, Grace A. Adegoye, Terezie Tolar-Peterson

BioMedicine

Objectives: Bitter taste perception affects food preference, eating behavior, and nutrient intake. The purpose of this study was to investigate the contribution of bitter taste gene polymorphisms to body fatness as measured by percentage of body fat.

Method: Three common single nucleotide polymorphisms (SNPs) of the TAS2R38 gene which result in amino acid changes in the protein (A49P, V262A, and I296V), were studied in three racially diverse groups: European Americans n=313, African Americans n=109, and Asians n=234.

Results: The allele frequencies of the three SNPs were similar to previous studies. The rare haplotypes, AAI and AAV, were found in high …

Genomic Education – Bench To Bedside: A Novel Approach To Teaching Genetic Diagnosis, J. Keith Williams, Michael M. Segal, Lynn K. Feldman

Internet Journal of Allied Health Sciences and Practice

Problem: Teaching genetic diagnosis is required in all medical schools and physician assistant programs. However, with thousands of relevant findings and thousands more rare diseases, lectures and narrative resources are inadequate for the task. Whatever information that is taught is easily forgotten and does not carry over into the clinic. Many rare disease patients suffer through “diagnostic odysseys” (3 to 30 years to correct diagnosis). Approach: We used a commercially available diagnostic decision support system (DDSS) that encompasses all Mendelian disorders with known genes, together with other conditions in their differential diagnosis, and a case-based educational approach to teach diagnostic …

Goblet Cell Carcinoma Of The Appendix: A Case Report On Goblet Cell Carcinoid, Sheliza Kabani, Aubtin Saedi, Austin Lehr, Lina O'Brien

HCA Healthcare Journal of Medicine

Goblet cell carcinoid of the appendix is a rare neoplasm with histological features of both neuroendocrine and adenocarcinomas. The combination of its aggressive behavior, infrequent occurrence, and variable clinical presentation convolutes the management of this tumor. We report the case of a 75-year-old female presenting with acute appendicitis. A laparoscopic appendectomy was performed. The pathology report showed goblet cell carcinoid at the base of the appendix with involvement of the proximal surgical margins. At her postoperative visit, the patient’s pathology report and options for management were reviewed, and the patient agreed to proceed with a right hemicolectomy 8-10 weeks after …

A Case Of Simpson-Golabi-Behmel Syndrome Presenting With Cutaneous Findings, Tessa Mullins, Abigail Russell, Chad Johnston

HCA Healthcare Journal of Medicine

Simpson-Golabi-Behmel syndrome is a rare, X-linked recessive syndrome associated with mutations in the genes encoding glypican 3 (GPC3). The majority of cases have been described in pediatric males, with those affected showing manifestations of overgrowth, congenital heart defects, and increased incidence of neoplasia. Due to the X-linked nature of this disorder, penetrance is not well understood in female cases. Very few cases of female presentations of Simpson-Golabi-Behmel syndrome have been described, and this case highlights that there may be an association between mutated GPC3 carrier status and other cancers. We present a case of GPC3 gene mutation suggestive …

Tumor Necrosis Factor Alpha Snp Variant In Promoter Region G308a, Cause Preeclampsia During Pregnancy In Pakistani Women, A Case Control Study, Azizah Ziauddin, Sadia Ahmad, Asad Iqbal, Abdul Majid Khan, Shahid Mahmood Baig

Journal of Bioresource Management

Preeclampsia (PE) is a very common critical condition during pregnancy. As PE is a high-risk condition during pregnancy, occurring in 25% of all pregnancies, worldwide. In women with PE there is an increase in hypertension and albuminuria. Elevated blood pressure can be life-threatening after 20^th week of pregnancy. Single nucleotide variation in gene sequence can be disease causing, among these pathogenic SNPs, a variant in TNF-α, G308A is analyzed in many studies as a causative variant to cause preeclampsia. In this case control study fifty patients and fifty healthy individuals were enrolled for analysis of TNF-α promoter region …

Genetic Duties, Jessica L. Roberts, Alexandra L. Foulkes

William & Mary Law Review

Most of our genetic information does not change, yet the results of our genetic tests might. Labs reclassify genetic variants in response to advances in genetic science. As a result, a person who took a test in 2010 could take the same test with the same lab in 2020 and get a different result. However, no legal duty requires labs or physicians to inform patients when a lab reclassifies a variant, even if the reclassification communicates clinically actionable information. This Article considers the need for such duties and their potential challenges. In so doing, it offers much-needed guidance to physicians …

Immunohistochemical Pattern– A Prognostic Factor For Synchronous Gastrointestinal Cancer, Catalin Alius, Catalin Gabriel Cirstoveanu, Cristinel Dumitru Badiu, Valeriu Ardeleanu, Vasile Adrian Dumitru

Journal of Mind and Medical Sciences

Recent advancements in medical genetics and molecular biology are reflected in the modern understanding and approach to colorectal carcinoma (CRC). Understanding the cellular mechanisms and mutational patterns that promote carcinogenesis could enhance the predictive accuracy of the TNM classification. Furthermore, this will allow for a much more documented stratification and tailored oncological treatment. This paper presents an illustrative case of a relatively young patient (50 years old) with no family history of cancer who was diagnosed with four synchronous gastrointestinal (GI) adenocarcinomas displaying a wild type P53, negative BRAF testing, and mutated MLH1 and PMS2 proteins. This case report contributes …

A Novel Methodology To Identify The Primary Topics Contained Within The Covid-19 Research Corpus, Allen Crane, Brock Freidrich, William Fehlman, Igor Frolow, Daniel W. Engels

SMU Data Science Review

In this paper, we present a novel framework and system for the identification of primary research topics from within a corpus of related publications, the classification of individual publications according to these topics, and the results of the application of our framework and system to the COVID-19 Open Research Dataset (CORD-19). CORD-19 is a corpus of published peer reviewed and pre-peer reviewed articles related to the coronavirus that causes COVID-19. Using machine learning techniques, such as Non-negative Matrix Factorization for Natural Language Processing and a Bayesian classifier, we developed a novel framework and system that automatically extracts sparse and meaningful …

Understanding Medical Mistrust In Black Women At Risk Of Brca 1/2 Mutations, Arnethea L. Sutton, Jun He, Erin Tanner, Megan C. Edmonds, Alesha Henderson, Alejandra Hurtado De Mendoza, Vanessa B. Sheppard

Journal of Health Disparities Research and Practice

The benefits of genetic counseling and testing for hereditary breast and/or ovarian cancer (HBOC) are well documented; however, Black women are less likely to use these services compared to White women. Mistrust of the medical system has been associated with Black women’s use of genetic counseling and testing (GCT). However, relatively little is known about the correlates of medical mistrust in Black women at increased risk of HBOC. In this study, we examined the prevalence and predictors of medical mistrust in 94 Black women at-risk of HBOC. Most women were married (48.7%) and had at least some collegiate education (57.1%). …

Genetic Variations In A Cytochrome P450 Enzyme And The Effects On Clopidogrel Bioactivation And Metabolism, Maryanne Ventura, Lauren Desko, Kimberly Gathers, Ashley Overy, David Kisor

Pharmacy and Wellness Review

Clopidogrel, the top prescribed antiplatelet medication for individuals who have experienced a myocardial infarction or cerebral vascular accident or who have peripheral arterial disease, is administered orally as a prodrug. It relies on hepatic metabolism through cytochrome P450 enzymes for conversion to its active form. Current research shows that allelic variation m the gene coding for CYP2C19 is the main factor contributing to the variability of response associated with clopidogrel treatment. Through the promotion of genetic testing for variability in the CYP2C19 gene and competently interpreting test results, pharmacists have the opportunity to use these findings to significantly impact clopidogrel …

Pharmacogenomics: Your Medical Identity, Hilary Stewart, Lisa Berni, Tyler Bulcher, Joel Rittenhouse, Ryan W. Naseman, Jon E. Sprague

Pharmacy and Wellness Review

Pharmacogenomics, the fusion of pharmacology and genomics, shows strong potential to solve many of today's dosing problems. lnter-patient dosing requirements, mainly due to genetic variability between patients, represent significant challenges for prescribers. Certain receptors, drug-targeted proteins, drug-transport mechanisms and drug-metabolizing enzymes are genetically established. Hence, any defect, absence or abnormality in the gene could alter how an affected individual will respond to a given drug. Due to advancements in technology, health care professionals who utilize pharmacogenomics may assess a patient's genetic profile and determine a predicted response to specific medications. This may result in potentially optimal dosing at the onset …

Acute Diagnosis Of Wilson’S Disease In A Teenage Patient, Sarah Irvin, Ryan Mccarthy

Marshall Journal of Medicine

Wilson’s Disease, a rare autosomal recessive genetic disease, is caused by a mutation in the ATP7B enzyme gene. Without this enzyme, copper builds up in the brain, liver, and cornea causing a multitude of symptoms. It is important to consider Wilson’s disease because the prognosis is dependent on timely diagnosis. This is an interesting case of a 19-year-old male who presented with suicidal thoughts and rapid weight loss. After many months and an extensive work-up, Wilson’s Disease was diagnosed. Due to his rapid decline, he was transferred to a larger university healthcare center where he is currently enrolled in clinical …

Genetic Predispositions To Opioid Addiction, Legislative Action And Implications To Pharmacy Practice, Adam N. Trimble, David N. Jones, Courtney L. Salvino, Michael M. Milks, David Kisor

Pharmacy and Wellness Review

Prescription pain-relievers can be powerfully effective agents in the treatment of moderate to severe pain; however, these drugs are also strongly associated with drug abuse and addiction. In the brain, opioid analgesics bind to various receptors in the mesocorticolimbic dopaminergic pathways, which play a multifaceted interaction of role in reward. Several specific single nucleotide polymorphisms (SNPs) have been identified as potential genetic factors that increase an individual's risk for addiction; however, confounding studies and lack of large trials prohibit definitive conclusions from being drawn. As a result of genetic testing, federal and state laws have been enacted to protect individuals …

Pharmacogenetics: Where Are We Now?, Brittany Dye, Megan Meyer, Vincent Wu, Michael D. Kaine

Pharmacy and Wellness Review

No abstract provided.

Antidepressant Dosing In Major Depression: A Pharmacogenomic Approach, Morgan Homan, Haval Norman, Victoria Cho, Yousif Rojeab

Pharmacy and Wellness Review

Major depressive disorder (MDD) is the most predominant mental disorder in the United States, with serious and costly health risks if not successfully managed. Pharmacotherapy is a standard option for MDD treatment, but patients often require extensive therapy adjustments to find a suitable regimen. Pharmacogenomics may enable greater precision in antidepressant therapy. Genotypic variations in CYP2D6 and CYP2C19 metabolic enzymes are reliable predictors of serum drug concentration, but the complex dose-response relationship of antidepressants prevents such variations from predicting therapy success. Additionally, ABCBl has been examined for its role in P-glycoprotein efflux of antidepressants in the brain, yet it is …

The Effect Of Cyp3a5 Polymorphism On Kidney Transplant Recipients Given Tacrolimus, Samia Alam, Sunitha Johns, Haval Norman, Brian Heilbronner, Yousif Rojeab

Pharmacy and Wellness Review

Tacrolimus, an immunosuppressant agent indicated for organ transplants, is commonly administered to reduce the risk of renal graft rejection in patients with chronic kidney disease (CKD) and end stage renal disease (ESRD). Due to its narrow therapeutic index and high inter-patient variability, studies have suggested that CYP3A5-based dosing provides specialized regimens which may significantly improve the chances of achieving therapeutic concentrations. According to the Clinical Pharmacogenetics Implementation Consortium (CPIC) recommendations, extensive (CYP3A5*1/*1) and intermediate metabolizers (CYP3A5*1/*3) require a higher initial dose while poor metabolizers (CYP3A5*3/*3) require a lower initial dose in order to achieve target tacrolimus concentrations. Studies concluded that …

Programmed Death Pathway Inhibition: Emerging Therapeutic Options For Treatment Of Advanced Or Refractory Cancers, Katherine Elsass, Morgan Homan, Jana Randolph, Brendan Rasor, David Kinder

Pharmacy and Wellness Review

The programmed death-1 (PD-1) pathway has a significant role in the promotion of immune tolerance. The PD-1 receptor ligands are normally expressed on various inactive immune cells. When cancer cells express these ligands, they are able to interact with active T and B lymphocytes to induce this tolerance. Nivolumab and pembrolizumab are two recently approved agents that act to disrupt this binding and facilitate an immune response against cancer cells. Numerous trials, including KEYNOTE-002 and CheckMate 063, have demonstrated the superior safety and efficacy of these drugs in patients with advanced or refractory cancers. Initially approved for the treatment of …

Pharmacogenetics: Cyps, Nat2 And 5-Htt Related To Antidepressants, Molly Kulp, Armond Cosiano, Kevin Krivanek, Amanda Lanker, Taylor Roberson, David F. Kisor

Pharmacy and Wellness Review

Pharmacogenetics (PGt), the study of a gene's influence on patient response to a drug, shows strong potential for explaining issues with efficacy related to antidepressant medications. Each year, antidepressants are one of the most commonly prescribed medications due to the millions of Americans affected by depression. Importantly, it is recognized that there is wide interpatient variability in drug response to antidepressants caused by genetic mutations, which can alter the pharmacodynamic (PD) and pharmacokinetic (PK) properties of various drugs used to treat depression. Proteins that are mainly involved in how patients respond to medications include receptors, drug-targeted proteins, drug transport proteins …