Browsing by Subject "Genetic testing"

Now showing 1 - 10 of 46
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    Assessing parental understanding of variant reclassification in pediatric neurology and developmental pediatrics clinics
    (Springer, 2021) Margolin, Amy; Helm, Benjamin M.; Treat, Kayla; Prucka, Sandra K.; Halverson, Colin M.E.; Medical and Molecular Genetics, School of Medicine
    Improvements in technology used for genetic testing have yielded an increased numbers of variants that are identified, each with a potential to return uninformative results. While some genetics providers may expect patients to be responsible for staying abreast of updates to their genetic testing results, it is unknown whether patients are even aware of the possibility of variant reclassification. Little research has assessed the comprehension and attitudes of parents of pediatric patients regarding reclassification of variants of uncertain significance (VUS). Semi-structured telephone interviews were conducted with parents (n = 15) whose children received a VUS from genetic testing in either the pediatric neurogenetics or developmental pediatrics clinics at Riley Hospital for Children in Indianapolis, Indiana. Most participants expressed understanding of the uncertainty surrounding their child's VUS test result. However, nearly half of participants shared that they had no prior knowledge of its potential reclassification. When asked whose responsibility it is to keep informed about changes to their child's VUS status, some participants stated that it belonged solely to healthcare providers - a distinctive finding of our study - whereas others felt that it was a joint responsibility between providers and the parents. We additionally found that some patients desire a support group for individuals with VUS. These results provide insight into the importance of pretest genetic counseling and the need for increased social and informational support for parents of children who receive inconclusive genetic testing results. We conclude that relying solely on the patient or guardian to manage uncertain results may be insufficient.
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    Autosomal Dominant Tubulointerstitial Kidney Disease: A New Tool to Guide Genetic Testing
    (Elsevier, 2020-09) LaFavers, Kaice A.; El-Achkar, Tarek M.; Medicine, School of Medicine
    Autosomal dominant tubulointerstitial disease (ADTKD) is a dominantly inherited progressive nonglomerular disease. Several factors, such as a nonspecific clinical presentation and relative rarity, impede the phenotyping of ADTKD into clinically relevant subtypes and impair the appropriate implementation of genetic testing. The study by Olinger et al. describes the largest multicenter ADTKD cohort, which is likely to become a key resource. The authors also provide a new clinical tool that could guide diagnosis and genetic testing.
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    Breast Cancer Germline Genetic Counseling and Testing for Populations of African Heritage Globally: A Scoping Review on Research, Practice, and Bioethical Considerations
    (American Society of Clinical Oncology, 2023) Iwai, Yoshiko; Toumbo, Kadiata; Zuze, Takondwa; Morgan, Jenny S.; Simwinga, Lusayo; Wright, Sarah T.; Fedoriw, Yuri; Oladeru, Oluwadamilola T.; Balogun, Onyinye D.; Roberson, Mya L.; Olopade, Olufunmilayo I.; Tomoka, Tamiwe; Elmore, Shekinah N. C.; Community and Global Health, Richard M. Fairbanks School of Public Health
    Purpose: Despite the disproportionately high risk of breast cancer among women of African heritage, little is known about the facilitators and barriers to implementing germline genetic testing and counseling (GT/C). Methods: This scoping review followed guidelines recommended by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews. Published manuscripts from database inception through 2021 were sourced from PubMed, Cumulative Index to Nursing and Allied Health Literature via EBSCO, Embase, Cochrane Library, and Scopus. Search terms were used to retrieve articles addressing (1) African heritage, (2) breast cancer, and (3) GT or GC. The screening involved abstract and title review and full-text review. Data were extracted for all articles meeting the inclusion criteria. Results: A total of 154 studies were included. Most studies that took place were conducted in the United States (71.4%), and most first authors (76.9%) were from the United States. GT was conducted in 73 (49.7%) studies. BRCA1/BRCA2 were the most commonly studied genes for germline mutations. GC was conducted in 49 studies (33.3%), and perspectives on GC were evaluated in 43 (29.3%). The use of racial/ethnic categories varied broadly, although African American was most common (40.1%). Racism was mentioned in three studies (2.0%). Conclusion: There is a growing body of literature on GT/C for breast cancer in women of African heritage. Future studies on GT/C of African populations should consider increased clarity around racial/ethnic categorizations, continued community engagement, and intentional processes for informed consent.
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    A Case for Inclusion of Genetic Counselors in Cardiac Care
    (Wolters Kluwer, 2016-03) Arscott, Patricia; Caleshu, Colleen; Kotzer, Katrina; Kreykes, Sarah; Kruisselbrink, Teresa; Orland, Kate; Rigelsky, Christina; Smith, Emily; Spoonamore, Katherine; Larsen Haidle, Joy; Marvin, Monica; Ackerman, Michael J.; Hadi, Azam; Mani, Arya; Ommen, Steven; Cherny, Sara; Department of Medicine, IU School of Medicine
    Recent advances in genetic testing for heritable cardiac diseases have led to an increasing involvement of the genetic counselor in cardiology practice. We present a series of cases collected from a nationwide query of genetics professionals regarding issues related to cost and utilization of genetic testing. Three themes emerged across cases: (1) choosing the most appropriate genetic test, (2) choosing the best person to test, and (3) interpreting results accurately. These cases demonstrate that involvement of a genetic counselor throughout the evaluation, diagnosis, and continuing management of individuals and families with inherited cardiovascular conditions helps to promote the efficient use of healthcare dollars.
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    Characterization of 137 Genomic DNA Reference Materials for 28 Pharmacogenetic Genes: A GeT-RM Collaborative Project
    (Elsevier, 2016-01) Pratt, Victoria M.; Everts, Robin E.; Aggarwal, Praful; Beyer, Brittany N.; Broeckel, Ulrich; Epstein-Baak, Ruth; Hujsak, Paul; Kornreich, Ruth; Liao, Jun; Lorier, Rachel; Scott, Stuart A.; Smith, Chingying Huang; Toji, Lorraine H.; Turner, Amy; Kalman, Lisa V.; Department of Medical and Molecular Genetics, IU School of Medicine
    Pharmacogenetic testing is increasingly available from clinical laboratories. However, only a limited number of quality control and other reference materials are currently available to support clinical testing. To address this need, the Centers for Disease Control and Prevention-based Genetic Testing Reference Material Coordination Program, in collaboration with members of the pharmacogenetic testing community and the Coriell Cell Repositories, has characterized 137 genomic DNA samples for 28 genes commonly genotyped by pharmacogenetic testing assays (CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4, CYP3A5, CYP4F2, DPYD, GSTM1, GSTP1, GSTT1, NAT1, NAT2, SLC15A2, SLC22A2, SLCO1B1, SLCO2B1, TPMT, UGT1A1, UGT2B7, UGT2B15, UGT2B17, and VKORC1). One hundred thirty-seven Coriell cell lines were selected based on ethnic diversity and partial genotype characterization from earlier testing. DNA samples were coded and distributed to volunteer testing laboratories for targeted genotyping using a number of commercially available and laboratory developed tests. Through consensus verification, we confirmed the presence of at least 108 variant pharmacogenetic alleles. These samples are also being characterized by other pharmacogenetic assays, including next-generation sequencing, which will be reported separately. Genotyping results were consistent among laboratories, with most differences in allele assignments attributed to assay design and variability in reported allele nomenclature, particularly for CYP2D6, UGT1A1, and VKORC1. These publicly available samples will help ensure the accuracy of pharmacogenetic testing.
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    Characterization of Reference Materials for CYP3A4 and CYP3A5: A GeT-RM Collaborative Project
    (Elsevier, 2023) Gaedigk, Andrea; Boone, Erin C.; Turner, Amy J.; van Schaik, Ron H.N.; Cheranova, Dilyara; Wang, Wendy Y.; Broeckel, Ulrich; Granfield, Caitlin A.; Hodge, Jennelle C.; Ly, Reynold C.; Lynnes, Ty C.; Mitchell, Matthew W.; Moyer, Ann M.; Oliva, Jason; Kalman, Lisa V.; Medical and Molecular Genetics, School of Medicine
    Pharmacogenetic testing for CYP3A4 is increasingly provided by clinical and research laboratories; however, only a limited number of quality control and reference materials are currently available for many of the CYP3A4 variants included in clinical tests. To address this need, the Division of Laboratory Systems, CDC-based Genetic Testing Reference Material Coordination Program (GeT-RM), in collaboration with members of the pharmacogenetic testing and research communities and the Coriell Institute for Medical Research, has characterized 30 DNA samples derived from Coriell cell lines for CYP3A4. Samples were distributed to five volunteer laboratories for genotyping using a variety of commercially available and laboratory-developed tests. Sanger and next-generation sequencing were also utilized by some of the laboratories. Whole-genome sequencing data from the 1000 Genomes Projects were utilized to inform genotype. Twenty CYP3A4 alleles were identified in the 30 samples characterized for CYP3A4: CYP3A4∗4, ∗5, ∗6, ∗7, ∗8, ∗9, ∗10, ∗11, ∗12, ∗15, ∗16, ∗18, ∗19, ∗20, ∗21, ∗22, ∗23, ∗24, ∗35, and a novel allele, CYP3A4∗38. Nineteen additional samples with preexisting data for CYP3A4 or CYP3A5 were re-analyzed to generate comprehensive reference material panels for these genes. These publicly available and well-characterized materials can be used to support the quality assurance and quality control programs of clinical laboratories performing clinical pharmacogenetic testing.
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    Clinical and educational impact of pharmacogenomics testing: a case series from the INGENIOUS trial
    (Future Medicine, 2017-06) Pierson, Rebecca C.; Gufford, Brandon T.; Desta, Zeruesenay; Eadon, Michael T.; Medicine, School of Medicine
    Pharmacogenomic testing has become increasingly widespread. However, there remains a need to bridge the gap between test results and providers lacking the expertise required to interpret these results. The Indiana Genomics Implementation trial is underway at our institution to examine total healthcare cost and patient outcomes after genotyping in a safety-net healthcare system. As part of the study, trial investigators and clinical pharmacology fellows interpret genotype results, review patient histories and medication lists and evaluate potential drug-drug interactions. We present a case series of patients in whom pharmacogenomic consultations aided providers in appropriately applying pharmacogenomic results within the clinical context. Formal consultations not only provide valuable patient care information but educational opportunities for the fellows to cement pharmacogenomic concepts.
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    Clinical Genetic and Genomic Testing in Congenital Heart Disease and Cardiomyopathy
    (MDPI, 2024-04-26) Pidaparti, Mahati; Geddes, Gabrielle C.; Durbin, Matthew D.; Pediatrics, School of Medicine
    Congenital heart disease (CHD) and cardiomyopathies are the leading cause of morbidity and mortality worldwide. These conditions are often caused by genetic factors, and recent research has shown that genetic and genomic testing can provide valuable information for patient care. By identifying genetic causes, healthcare providers can screen for other related health conditions, offer early interventions, estimate prognosis, select appropriate treatments, and assess the risk for family members. Genetic and genomic testing is now the standard of care in patients with CHD and cardiomyopathy. However, rapid advances in technology and greater availability of testing options have led to changes in recommendations for the most appropriate testing method. Several recent studies have investigated the utility of genetic testing in this changing landscape. This review summarizes the literature surrounding the clinical utility of genetic evaluation in patients with CHD and cardiomyopathy.
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    Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2D6, OPRM1, and COMT Genotypes and Select Opioid Therapy
    (Wiley, 2021) Crews, Kristine R.; Monte, Andrew A.; Huddart, Rachel; Caudle, Kelly E.; Kharasch, Evan D.; Gaedigk, Andrea; Dunnenberger, Henry M.; Leeder, J. Steven; Callaghan, John T.; Samer, Caroline Flora; Klein, Teri E.; Haidar, Cyrine E.; Van Driest, Sara L.; Ruano, Gualberto; Sangkuhl, Katrin; Cavallari, Larisa H.; Müller, Daniel J.; Prows, Cynthia A.; Nagy, Mohamed; Somogyi, Andrew A.; Skaar, Todd C.; Medicine, School of Medicine
    Opioids are mainly used to treat both acute and chronic pain. Several opioids are metabolized to some extent by CYP2D6 (codeine, tramadol, hydrocodone, oxycodone and methadone). Polymorphisms in CYP2D6 have been studied for an association with the clinical effect and safety of these drugs. Other genes which have been studied for their association with opioid clinical effect or adverse events include OPRM1 (mu receptor) and COMT (catechol-O-methyltransferase). This guideline updates and expands the 2014 Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2D6 genotype and codeine therapy and includes a summation of the evidence describing the impact of CYP2D6, OPRM1 and COMT on opioid analgesia and adverse events. We provide therapeutic recommendations for the use of CYP2D6 genotype results for prescribing codeine and tramadol and describe the limited and/or weak data for CYP2D6 and hydrocodone, oxycodone and methadone and for OPRM1 and COMT for clinical use.
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    A Comprehensive Clinical Genetics Approach to Critical Congenital Heart Disease in Infancy
    (Elsevier, 2020-12) Shikany, Amy R.; Landis, Benjamin J.; Parrott, Ashley; Miller, Erin M.; Coyan, Alyxis; Walters, Lauren; Hinton, Robert B.; Goldenberg, Paula; Ware, Stephanie M.; Medical and Molecular Genetics, School of Medicine
    Objective: To investigate the frequency of genetic diagnoses among infants with critical congenital heart disease (CHD) using a comprehensive cardiovascular genetics approach and to identify genotype-phenotype correlations. Study design: A retrospective chart review of patients evaluated by cardiovascular genetics in a pediatric cardiac intensive care unit from 2010 to 2015 was performed. Infants with CHD who were <1 month of age were included. CHD was classified using structured phenotype definitions. Cardiac and noncardiac phenotypes were tested for associations with abnormal genetic testing using χ1 and Fisher exact tests. Results: Genetic evaluation was completed in 293 infants with CHD, of whom 213 had isolated congenital heart disease (iCHD) and 80 had multiple congenital anomalies. Overall, the yield of abnormal genetic testing was 26%. The multiple congenital anomalies cohort had a greater yield of genetic testing (39%) than the iCHD cohort (20%) (OR 2.7). Using a non-hierarchical CHD classification and excluding 22q11.2 deletion and common aneuploidies, right ventricular obstructive defects were associated with abnormal genetic testing (P = .0005). Extracardiac features associated with abnormal genetic testing included ear, nose, and throat (P = .003) and brain (P = .0001) abnormalities. A diagnosis of small for gestational age or intrauterine growth retardation also was associated with abnormal genetic testing (P = .0061), as was presence of dysmorphic features (P = .0033, OR 3.5). Infants without dysmorphia with iCHD or multiple congenital anomalies had similar frequencies of abnormal genetic testing. Conclusions: The present study provides evidence to support a comprehensive cardiovascular genetics approach in evaluating infants with critical CHD while also identifying important genotype-phenotype considerations.