21 results on '"Priyanka, Ahimaz"'
Search Results
2. Exploring the role of genetic counselors in immunology: A study of immunologist and allergist perspectives
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Priyanka Ahimaz, Jennah C. Foltz, Meredith J. Ross, Michelle E. Florido, Monisha Sebastin, and Joyce E. Yu
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Immunology and Allergy - Published
- 2023
3. Delineation of a KDM2B-related neurodevelopmental disorder and its associated DNA methylation signature
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Richard H. van Jaarsveld, Jack Reilly, Marie-Claire Cornips, Michael A. Hadders, Emanuele Agolini, Priyanka Ahimaz, Kwame Anyane-Yeboa, Severine Audebert Bellanger, Ellen van Binsbergen, Marie-Jose van den Boogaard, Elise Brischoux-Boucher, Raymond C. Caylor, Andrea Ciolfi, Ton A.J. van Essen, Paolo Fontana, Saskia Hopman, Maria Iascone, Margaret M. Javier, Erik-Jan Kamsteeg, Jennifer Kerkhof, Jun Kido, Hyung-Goo Kim, Tjitske Kleefstra, Fortunato Lonardo, Abbe Lai, Dorit Lev, Michael A. Levy, M.E. Suzanne Lewis, Angie Lichty, Marcel M.A.M. Mannens, Naomichi Matsumoto, Idit Maya, Haley McConkey, Andre Megarbane, Vincent Michaud, Evelina Miele, Marcello Niceta, Antonio Novelli, Roberta Onesimo, Rolph Pfundt, Bernt Popp, Eloise Prijoles, Raissa Relator, Sylvia Redon, Dmitrijs Rots, Karen Rouault, Ken Saida, Jolanda Schieving, Marco Tartaglia, Romano Tenconi, Kevin Uguen, Nienke Verbeek, Christopher A. Walsh, Keren Yosovich, Christopher J. Yuskaitis, Giuseppe Zampino, Bekim Sadikovic, Mariëlle Alders, Renske Oegema, Human Genetics, ACS - Pulmonary hypertension & thrombosis, Amsterdam Reproduction & Development (AR&D), and Human genetics
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MDEMs ,All institutes and research themes of the Radboud University Medical Center ,Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7] ,KDM2B ,Methylation signatures ,Neurodevelopmental disorders ,Human Genetics ,Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3] ,Genetics (clinical) ,Sensory disorders Donders Center for Medical Neuroscience [Radboudumc 12] - Abstract
Contains fulltext : 290808.pdf (Publisher’s version ) (Open Access) PURPOSE: Pathogenic variants in genes involved in the epigenetic machinery are an emerging cause of neurodevelopment disorders (NDDs). Lysine-demethylase 2B (KDM2B) encodes an epigenetic regulator and mouse models suggest an important role during development. We set out to determine whether KDM2B variants are associated with NDD. METHODS: Through international collaborations, we collected data on individuals with heterozygous KDM2B variants. We applied methylation arrays on peripheral blood DNA samples to determine a KDM2B associated epigenetic signature. RESULTS: We recruited a total of 27 individuals with heterozygous variants in KDM2B. We present evidence, including a shared epigenetic signature, to support a pathogenic classification of 15 KDM2B variants and identify the CxxC domain as a mutational hotspot. Both loss-of-function and CxxC-domain missense variants present with a specific subepisignature. Moreover, the KDM2B episignature was identified in the context of a dual molecular diagnosis in multiple individuals. Our efforts resulted in a cohort of 21 individuals with heterozygous (likely) pathogenic variants. Individuals in this cohort present with developmental delay and/or intellectual disability; autism; attention deficit disorder/attention deficit hyperactivity disorder; congenital organ anomalies mainly of the heart, eyes, and urogenital system; and subtle facial dysmorphism. CONCLUSION: Pathogenic heterozygous variants in KDM2B are associated with NDD and a specific epigenetic signature detectable in peripheral blood. 01 januari 2023
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- 2023
4. A novel biallelic loss-of-function variant in
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Mythily, Ganapathi, Christie M, Buchovecky, Fernando, Cristo, Priyanka, Ahimaz, Carrie, Ruzal-Shapiro, Karen, Wou, José M, Inácio, Alejandro, Iglesias, José A, Belo, and Vaidehi, Jobanputra
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Heterozygote ,Mutation, Missense ,Humans ,Intercellular Signaling Peptides and Proteins ,Heterotaxy Syndrome - Abstract
The majority of heterotaxy cases do not obtain a molecular diagnosis, although pathogenic variants in more than 50 genes are known to cause heterotaxy. A heterozygous missense variant in
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- 2022
5. Assessment of the beliefs, needs, and expectations for genetic counseling of patients with hypermobile Ehlers-Danlos syndrome
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Priyanka Ahimaz, Tamar Kramer, Pooja Swaroop, McKenzie Mitchell, Rebecca Hernan, Kwame Anyane‐Yeboa, and Elaine M. Pereira
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Joint Instability ,Motivation ,Genetics ,Humans ,Ehlers-Danlos Syndrome ,Genetic Counseling ,Genetics (clinical) - Abstract
Ehlers-Danlos syndrome, hypermobility type (hEDS) is a heritable connective tissue disorder that currently does not have a known molecular etiology. Previous studies have explored the complex symptomology, clinical diagnosis, and psychological aspects of hEDS. Genetics providers currently aid in the diagnosis and management guidance of patients with hEDS, but there is limited data describing the needs and expectations of individuals with hEDS from a clinical genetics appointment. Our study sought to explore these items through the use of an online survey to assess participants' beliefs, needs and expectations (BNE) for genetic counseling as well as questions about demographics, hEDS symptoms, and current medical care. A total of 460 respondents with hEDS completed the survey. Most participants felt joint pain/weakness (n = 392; 88%) was one of the most disruptive symptoms of hEDS and 63% (n = 289) reported having psychiatric conditions. BNE scores were highest in two domains: expectations to have psychosocial concerns addressed during a genetic counseling appointment (mean score = 4.4/5; SD = 0.56) and desire for positive feelings after a genetic counseling session (mean score = 4.3/5; SD = 0.59). Participants who previously had genetic counseling felt less unsure about their diagnosis (p = 0.02) and had lower need for information about hEDS (p 0.001). Majority of participants did not feel that their doctors were knowledgeable about hEDS (n = 269; 58%) and strongly supported a multidisciplinary approach to their care (n = 445; 97%). This research provides a framework for genetics providers and other healthcare professionals to assess the needs and expectations of patients with hEDS and consider re-structuring their appointment formats to service this population.
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- 2022
6. Discovering the Developmental Basis of Trachea‐Esophageal Birth Defects: Evidence for Endosome‐opathies
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Nicole Edwards, Guojie Zhong, Priyanka Ahimaz, Alan Kenny, Paul Kingma, James Wells, Yufeng Shen, Wendy Chung, and Aaron Zorn
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Genetics ,Molecular Biology ,Biochemistry ,Biotechnology - Published
- 2022
7. A novel homozygous variant in TRAPPC2L results in a neurodevelopmental disorder and disrupts TRAPP complex function
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Priyanka Ahimaz, Yufeng Sheng, Jacob J. Hagen, Wendy K. Chung, Michael Sacher, Zaheer Valivullah, Volkan Okur, Mythily Ganapathi, Miroslav P. Milev, and Noraldin Al-Deri
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Adult ,Male ,0301 basic medicine ,Protein subunit ,DNA Mutational Analysis ,Vesicular Transport Proteins ,Article ,Structure-Activity Relationship ,03 medical and health sciences ,symbols.namesake ,0302 clinical medicine ,Neurodevelopmental disorder ,Genetics ,medicine ,Humans ,Missense mutation ,Genetic Predisposition to Disease ,Amino Acid Sequence ,Global developmental delay ,Age of Onset ,Alleles ,Genetic Association Studies ,Genetics (clinical) ,Whole genome sequencing ,biology ,Homozygote ,Membrane Transport Proteins ,Golgi apparatus ,medicine.disease ,Phenotype ,Pedigree ,030104 developmental biology ,TRAPP complex ,Amino Acid Substitution ,Haplotypes ,Neurodevelopmental Disorders ,Mutation ,symbols ,biology.protein ,Female ,Protein Multimerization ,030217 neurology & neurosurgery ,Protein Binding ,Transcription Factors - Abstract
BackgroundNext-generation sequencing has facilitated the diagnosis of neurodevelopmental disorders with variable and non-specific clinical findings. Recently, a homozygous missense p.(Asp37Tyr) variant in TRAPPC2L, a core subunit of TRAPP complexes which function as tethering factors during membrane trafficking, was reported in two unrelated individuals with neurodevelopmental delay, post-infectious encephalopathy-associated developmental arrest, tetraplegia and accompanying rhabdomyolysis.MethodsWe performed whole genome sequencing on members of an Ashkenazi Jewish pedigree to identify the underlying genetic aetiology of global developmental delay/intellectual disability in three affected siblings. To assess the effect of the identified TRAPPC2L variant, we performed biochemical and cell biological functional studies on the TRAPPC2L protein.ResultsA rare homozygous predicted deleterious missense variant, p.(Ala2Gly), in TRAPPC2L was identified in the affected siblings and it segregated with the neurodevelopmental phenotype within the family. Using a yeast two-hybrid assay and in vitro binding, we demonstrate that the p.(Ala2Gly) variant, but not the p.(Asp37Tyr) variant, disrupted the interaction between TRAPPC2L and another core TRAPP protein, TRAPPC6a. Size exclusion chromatography suggested that this variant affects the assembly of TRAPP complexes. Employing two different membrane trafficking assays using fibroblasts from one of the affected siblings, we found a delay in traffic into and out of the Golgi. Similar to the p.(Asp37Tyr) variant, the p.(Ala2Gly) variant resulted in an increase in the levels of active RAB11.ConclusionOur data fill in a gap in the knowledge of TRAPP architecture with TRAPPC2L interacting with TRAPPC6a, positioning it as a putative adaptor for other TRAPP subunits. Collectively, our findings support the pathogenicity of the TRAPPC2L p.(Ala2Gly) variant.
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- 2020
8. Clinical genetic counselor experience in the adoption of telehealth in the United States and Canada during the COVID-19 pandemic
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James Mirocha, Jessica Giordano, Daria Ma, Pooja Mohan, Priyanka Ahimaz, Lola Cook, and Stephanie A. Cohen
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medicine.medical_specialty ,Telemedicine ,Canada ,Coronavirus disease 2019 (COVID-19) ,Commute time ,business.industry ,Service delivery framework ,SARS-CoV-2 ,Genetic counseling ,education ,COVID-19 ,Telehealth ,United States ,Counselors ,Cross-Sectional Studies ,Family medicine ,Pandemic ,Clinical genetic ,Medicine ,Humans ,business ,Pandemics ,health care economics and organizations ,Genetics (clinical) - Abstract
The COVID-19 pandemic has significantly impacted the service delivery model (SDM) of clinical genetic counseling across the United States and Canada. A cross-sectional survey was distributed to 4,956 genetic counselors (GCs) from the American Board of Genetic Counselors and Canadian Association of Genetic Counselors mailing lists in August 2020 to assess the change in utilization of telehealth for clinical genetic counseling during the COVID-19 pandemic compared with prior to the pandemic. Data from 411 eligible clinical genetic counselors on GC attitudes and their experiences prior to and during the pandemic were collected and analyzed to explore the change in SDM, change in appointment characteristics, change in billing practices, GC perceived benefits and limitations of telehealth, and prediction of future trends in SDM in the post-pandemic era. The study showed the overall utilization of audiovisual and telephone encounters increased by 43.4% and 26.2%, respectively. The majority of respondents who provided audiovisual and telephone encounters reported increased patient volume compared with prior to the pandemic, with an average increase of 79.4% and 42.8%, respectively. There was an increase of 69.4% of GCs rendering genetic services from home offices. The percentage of participants who billed for telehealth services increased from 45.7% before the pandemic to 80.3% during the pandemic. The top GC perceived benefits of telehealth included safety for high-risk COVID patients (95.2%) and saved commute time for patients (94.7%). The top GC perceived limitations of telehealth included difficulty to conduct physician evaluation/coordinating with healthcare providers (HCP) (73.7%) and difficulty addressing non-English speaking patients (68.5%). Overall, 89.6% of GCs were satisfied with telehealth; however, 55.3% reported uncertainty whether the newly adopted SDM would continue after the pandemic subsides. Results from this study demonstrate the rapid adoption of telehealth for clinical genetic counseling services as a result of the COVID-19 pandemic, an increase in billing for these services, and support the feasibility of telehealth for genetic counseling as a longer term solution to reach patients who are geographically distant.
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- 2021
9. PPA2-associated sudden cardiac death
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Charlotte V. Y. Knowles, Anil Kanthi, Carolyn Tysoe, Georgia Spentzou, Claire L. S. Turner, Jan A Till, Liza K. Phillips, Anne Moreau de Bellaing, Diptendu Chatterjee, Alexandre Janin, Paul French, Tamara T. Koopmann, Anju Shukla, Melanie T. Achleitner, Loïc de Pontual, Matthew S. Edwards, Deborah J. Morris-Rosendahl, Noha Elserafy, Kirti Mittal, Jessie Cameron, Wendy K. Chung, Saskia B. Wortmann, Sajel L Kana, Kit Doudney, Robert G. Weintraub, Peter M George, Priyanka Ahimaz, Kyla Dunn, Ona Faye-Petersen, Katta M. Girisha, Hannah L. Kennedy, Kate S Lichkus, Alexa Kidd, Sumith Parikh, Jason D. Merker, Megan E. Grove, Ruth McGowan, Laura Brett, Anna C.E. Hurst, Jeanne Amiel, Bindu Parayil Sankaran, Dianna G. Fisk, Clémantine Dimartino, Charlotte L. Alston, Michelle L. Thompson, Johannes A. Mayr, Tessa Homfray, Alan Ma, Robert McFarland, Muhammad A Rafiq, Anne Guimier, Robert M Hamilton, Christian Turner, Karen McLeod, Christopher T. Gordon, Robert W. Taylor, David R. Thorburn, Florence van den Broek, Carolyn Ellaway, and Fanny Bajolle
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Neurological signs ,medicine.medical_specialty ,Adolescent ,Cardiomyopathy ,Disease ,Article ,Sudden cardiac death ,Mitochondrial Proteins ,Internal medicine ,Humans ,Medicine ,Allele ,Alleles ,Genetics (clinical) ,Genetics & Heredity ,0604 Genetics ,Science & Technology ,business.industry ,Sudden cardiac arrest ,1103 Clinical Sciences ,Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6] ,medicine.disease ,DEFICIENCY ,Inorganic Pyrophosphatase ,Death, Sudden, Cardiac ,Child, Preschool ,Heart failure ,Mutation ,Alcohol intake ,medicine.symptom ,Cardiomyopathies ,business ,Life Sciences & Biomedicine - Abstract
Purpose Biallelic hypomorphic variants in PPA2, encoding the mitochondrial inorganic pyrophosphatase 2 protein, have been recently identified in individuals presenting with sudden cardiac death, occasionally triggered by alcohol intake or a viral infection. Here we report 20 new families harboring PPA2 variants. Methods Synthesis of clinical and molecular data concerning 34 individuals harboring five previously reported PPA2 variants and 12 novel variants, 11 of which were functionally characterized. Results Among the 34 individuals, only 6 remain alive. Twenty-three died before the age of 2 years while five died between 14 and 16 years. Within these 28 cases, 15 died of sudden cardiac arrest and 13 of acute heart failure. One case was diagnosed prenatally with cardiomyopathy. Four teenagers drank alcohol before sudden cardiac arrest. Progressive neurological signs were observed in 2/6 surviving individuals. For 11 variants, recombinant PPA2 enzyme activities were significantly decreased and sensitive to temperature, compared to wild-type PPA2 enzyme activity. Conclusion We expand the clinical and mutational spectrum associated with PPA2 dysfunction. Heart failure and sudden cardiac arrest occur at various ages with inter- and intrafamilial phenotypic variability, and presentation can include progressive neurological disease. Alcohol intake can trigger cardiac arrest and should be strictly avoided.
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- 2021
10. Impact of Genetic Testing for Cardiomyopathy on Emotional Well-Being and Family Dynamics: A Study of Parents and Adolescents
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Aijin Wang, Maya Sabatello, Paul F. Kantor, Stephanie M. Ware, Julia Wynn, Min Qian, Priyanka Ahimaz, Joseph W. Rossano, John J. Parent, Paul S. Appelbaum, Ashwin K. Lal, Ashley Parrott, Wendy K. Chung, Linda J. Addonizio, Kathryn C. Chatfield, Teresa M. Lee, Erin M. Miller, and Lisa Yue
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Male ,Parents ,Adolescent ,medicine.diagnostic_test ,Emotions ,Cardiomyopathy ,General Medicine ,medicine.disease ,Article ,Emotional well-being ,Family dynamics ,Surveys and Questionnaires ,Risk stratification ,medicine ,Humans ,Female ,Genetic Testing ,Family history ,Cardiomyopathies ,Child ,Psychology ,Clinical psychology ,Genetic testing - Abstract
Background: Genetic testing is indicated for children with a personal or family history of hereditary cardiomyopathy to determine appropriate management and inform risk stratification for family members. The implications of a positive genetic result for children can potentially impact emotional well-being. Given the nuances of cardiomyopathy genetic testing for minors, this study aimed to understand how parents involve their children in the testing process and investigate the impact of genetic results on family dynamics. Methods: A survey was distributed to participants recruited from the Children’s Cardiomyopathy Foundation and 7 North American sites in the Pediatric Cardiomyopathy Registry. The survey explored adolescent and parent participants’ emotions upon receiving their/their child’s genetic results, parent-child result communication and its impact on family functionality, using the McMaster Family Assessment Device. Results: One hundred sixty-two parents of minors and 48 adolescents who were offered genetic testing for a personal or family history of cardiomyopathy completed the survey. Parents whose child had cardiomyopathy were more likely to disclose positive diagnostic genetic results to their child ( P =0.014). Parents with unaffected children and positive predictive testing results were more likely to experience negative emotions about the result ( P ≤0.001) but also had better family functioning scores than those with negative predictive results ( P =0.019). Most adolescents preferred results communicated directly to the child, but parents were divided about whether their child’s result should first be released to them or their child. Conclusions: These findings have important considerations for how providers structure genetic services for adolescents and facilitate discussion between parents and their children about results.
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- 2021
11. Identification and validation of novel candidate risk genes in endocytic vesicular trafficking associated with esophageal atresia and tracheoesophageal fistulas
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C. Faure, William Middlesworth, Elizabeth A. Fialkowski, Julie Khlevner, Alan P. Kenny, Wendy K. Chung, David T. Schindel, S. Forlenza, G. Zhong, Priyanka Ahimaz, Paul S. Kingma, Aaron M. Zorn, Jacob J. Hagen, Nicole A. Edwards, Yufeng Shen, A. Kashyap, and M. El Fiky
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Proband ,Whole genome sequencing ,Genetics ,education.field_of_study ,Mutation rate ,Population ,Foregut ,Biology ,education ,Gene ,Phenotype ,Loss function - Abstract
Esophageal atresias/tracheoesophageal fistulas (EA/TEF) are rare congenital anomalies caused by aberrant development of the foregut. Previous studies indicate that rare or de novo genetic variants significantly contribute to EA/TEF risk, and most individuals with EA/TEF do not have pathogenic genetic variants in established risk genes. To identify novel genetic contributions to EA/TEF, we performed whole genome sequencing of 185 trios (probands and parents) with EA/TEF, including 59 isolated and 126 complex cases with additional congenital anomalies and/or neurodevelopmental disorders. There was a significant burden of protein altering de novo coding variants in complex cases (p=3.3e-4), especially in genes that are intolerant of loss of function variants in the population. We performed simulation analysis of pathway enrichment based on background mutation rate and identified a number of pathways related to endocytosis and intracellular trafficking that as a group have a significant burden of protein altering de novo variants. We assessed 18 variants for disease causality using CRISPR-Cas9 mutagenesis in Xenopus and confirmed 13 with tracheoesophageal phenotypes. Our results implicate disruption of endosome-mediated epithelial remodeling as a potential mechanism of foregut developmental defects. This research may have implications for the mechanisms of other rare congenital anomalies.
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- 2021
12. COVID contingencies: Early epicenter experiences of different genetics clinics at a New York City institution inform emergency adaptation strategies
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Rebecca Hernan, Jessica Giordano, Priyanka Ahimaz, Michele Disco, Erica Spiegel, Emily Griffin, Elizabeth Harrington, Elana Levinson, Carli Andrews, and Julia Wynn
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Telemedicine ,genetic services ,media_common.quotation_subject ,Genetic counseling ,Genetic Counseling ,Ambulatory Care Facilities ,Special Issues ,genetic counselors ,Adaptation, Psychological ,Health care ,Pandemic ,Institution ,Humans ,Sociology ,Situational ethics ,Pandemics ,Genetics (clinical) ,media_common ,Genetics ,Academic Medical Centers ,Special Issue ,business.industry ,Lived experience ,service delivery models ,COVID-19 ,Workflow ,lived experience ,New York City ,telemedicine ,business - Abstract
The unique situational challenges of the COVID‐19 pandemic have demanded creative modifications to the delivery of genetic services. Institutions across the country have adapted workflows to continue to provide quality care while minimizing the need for physical visits. As the first epicenter of the pandemic in the country, New York City healthcare workers and residents had to make rapid, unprecedented changes to their way of life. This article describes the workflow adaptations of genetic counselors across various clinical settings at New York Presbyterian/Columbia University Irving Medical Center, the largest provider of genetics care in New York City, during the height of the COVID‐19 pandemic. The authors observe how the adaptations impacted clinical care and the genetic counselors. Our lived experience and account can provide guidance for others during the current and future pandemics.
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- 2021
13. COVID-19’s Impact on Genetics at One Medical Center in New York
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Elaine M. Pereira, Priyanka Ahimaz, Carli Andrews, Kwame Anyane-Yeboa, Todor Arsov, Sara M. Berger, Ilana Chilton, Diana M. Cory, Wendy K. Chung, Katia R. Dergham, Michele M. Disco, Michelle E. Ernst, Tamar Forman, Stephanie Galloway, Alexa R. Geltzeiler, Jessica L. Giordano, Emily Griffin, Edwin Guzman, Nina Harkavy, Rebecca Hernan, Anah K. Hetzler, Alejandro Iglesias, Rupinder Kakar, Catherine Kentros, Thandiwe C. Khonje, Carrie Koval, Elana Levinson, Scott Robinson, Meredith J. Ross, Fatema Sadeque-Iqbal, Erica Spiegel, Elana Spitz, and Ronald J. Wapner
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medicine.medical_specialty ,2019-20 coronavirus outbreak ,Coronavirus disease 2019 (COVID-19) ,business.industry ,Genetics, Medical ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Comment ,New York ,COVID-19 ,Family medicine ,medicine ,Humans ,Center (algebra and category theory) ,Genetics(clinical) ,business ,Genetics (clinical) - Published
- 2020
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14. Bi-allelic missense disease-causing variants in RPL3L associate neonatal dilated cardiomyopathy with muscle-specific ribosome biogenesis
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Susanne Morlot, Juan Cabezas-Herrera, Teresa M Lee, Bernd Auber, Alexander von Gise, Holger Thiele, Arne Zibat, Mythily Ganapathi, Barry Honig, Francisco Martínez-Azorín, Yun Li, Peter Burfeind, Christie M. Buchovecky, María Sabater-Molina, Moisés Sorlí-García, Lukas Cyganek, Loukas Argyriou, Donald Petrey, Markus D. Siegelin, Alejandro D. Iglesias, Gerd Hasenfuss, Bernd Wollnik, Priyanka Ahimaz, and Gökhan Yigit
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Cardiomyopathy, Dilated ,Male ,Ribosomal Proteins ,Ribosomal Protein L3 ,Population ,Cardiomyopathy ,Mutation, Missense ,030204 cardiovascular system & hematology ,Biology ,Compound heterozygosity ,03 medical and health sciences ,0302 clinical medicine ,Ribosomal protein ,Genetics ,medicine ,Missense mutation ,Humans ,Exome ,education ,Muscle, Skeletal ,Gene ,Genetics (clinical) ,Alleles ,030304 developmental biology ,Original Investigation ,0303 health sciences ,education.field_of_study ,Eukaryotic Large Ribosomal Subunit ,Infant, Newborn ,Infant ,Heart ,Ribosomal RNA ,medicine.disease ,Pedigree ,Phenotype ,RNA ,Female ,Ribosomes - Abstract
Dilated cardiomyopathy (DCM) belongs to the most frequent forms of cardiomyopathy mainly characterized by cardiac dilatation and reduced systolic function. Although most cases of DCM are classified as sporadic, 20–30% of cases show a heritable pattern. Familial forms of DCM are genetically heterogeneous, and mutations in several genes have been identified that most commonly play a role in cytoskeleton and sarcomere-associated processes. Still, a large number of familial cases remain unsolved. Here, we report five individuals from three independent families who presented with severe dilated cardiomyopathy during the neonatal period. Using whole-exome sequencing (WES), we identified causative, compound heterozygous missense variants in RPL3L (ribosomal protein L3-like) in all the affected individuals. The identified variants co-segregated with the disease in each of the three families and were absent or very rare in the human population, in line with an autosomal recessive inheritance pattern. They are located within the conserved RPL3 domain of the protein and were classified as deleterious by several in silico prediction software applications. RPL3L is one of the four non-canonical riboprotein genes and it encodes the 60S ribosomal protein L3-like protein that is highly expressed only in cardiac and skeletal muscle. Three-dimensional homology modeling and in silico analysis of the affected residues in RPL3L indicate that the identified changes specifically alter the interaction of RPL3L with the RNA components of the 60S ribosomal subunit and thus destabilize its binding to the 60S subunit. In conclusion, we report that bi-allelic pathogenic variants in RPL3L are causative of an early-onset, severe neonatal form of dilated cardiomyopathy, and we show for the first time that cytoplasmic ribosomal proteins are involved in the pathogenesis of non-syndromic cardiomyopathies.
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- 2020
15. Impact of patient education videos on genetic counseling outcomes after exome sequencing
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Kwame Anyane-Yeboa, Catherine Au, Josue Natanael Martinez, Rebecca Hernan, Michelle Primiano, Robert L. Klitzman, Priyanka Ahimaz, Sara M. Berger, Edwin Guzman, Leyla Tabanfar, Wendy K. Chung, Alejandro D. Iglesias, Ilana Chilton, Laura Pisani, Julia Wynn, Ruth Ottman, Paul S. Appelbaum, Jessica E. Shaw, Jimmy Duong, Jasmin Roohi, Ashley Wilson, Megan T. Cho, Meredith Ross, Chana Ratner, and Emily Griffin
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Parents ,medicine.medical_specialty ,Genetic counseling ,Genetic counselors ,Patient education--Evaluation ,Article ,03 medical and health sciences ,0302 clinical medicine ,Patient Education as Topic ,Patient experience ,medicine ,Humans ,Exome ,Patient education--Audio-visual aids ,030212 general & internal medicine ,Routine care ,Exome sequencing ,030503 health policy & services ,General Medicine ,Counselors ,Family medicine ,0305 other medical science ,Psychology ,Video education ,Patient education - Abstract
Objective Growing use of clinical exome sequencing (CES) has led to an increased burden of genomic education. Self-guided educational tools can minimize the educational burden for genetic counselors (GCs). The effectiveness of these tools must be evaluated. Methods Parents of patients offered CES were randomized to watch educational videos before their visit or to receive routine care. Parents and GCs were surveyed about their experiences following the sessions. The responses of the video (n = 102) and no-video (n = 105) groups were compared. Results GCs reported no significant differences between parents in the video and no-video groups on genetics knowledge or CES knowledge. In contrast, parents’ scores on genetics knowledge questions were lower in the video than no-video group (p = 0.007). Most parents reported the videos were informative, and the groups did not differ in satisfaction with GCs or decisions to have CES. Conclusion GCs and parents perceived the videos to be beneficial. However, lower scores on genetics knowledge questions highlight the need for careful development of educational tools. Practice implications Educational tools should be developed and assessed for effectiveness with the input of all stakeholders before widespread implementation. Better measures of the effectiveness of these educational tools are needed.
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- 2020
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16. Examining the Psychosocial Impact of Genetic Testing for Cardiomyopathies
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Julia Wynn, Wendy K. Chung, Priyanka Ahimaz, David T. Holland, and Jimmy Duong
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Adult ,Male ,0301 basic medicine ,Genetic counseling ,Cardiomyopathy ,Genetic Counseling ,Disease ,030105 genetics & heredity ,Sudden cardiac death ,03 medical and health sciences ,Risk Factors ,medicine ,Humans ,Family ,Genetic Predisposition to Disease ,Genetic Testing ,Family history ,Genetics (clinical) ,Genetic testing ,medicine.diagnostic_test ,business.industry ,Hypertrophic cardiomyopathy ,Cardiomyopathy, Hypertrophic ,medicine.disease ,Cross-Sectional Studies ,Female ,Cardiomyopathies ,business ,Psychosocial ,Clinical psychology - Abstract
Inherited cardiomyopathies, including hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM), are the most common monogenic cause of cardiac disease and can rarely lead to sudden cardiac death (SCD). They are characterized by incomplete and age-dependent penetrance and are usually initially symptomatic in adulthood yet can present in childhood as well. Over 20 genes have been identified to cause HCM, and more than 40 genes are known to cause DCM. Genetic testing for these genes has been integrated into medical care; however, the psychological impact of genetic testing and the impact of the uncertainty that comes with receiving these results have not been well studied. This study surveyed 90 adult probands and relatives with a personal or family history of cardiomyopathy from a single hospital-based cardiac genetic program to determine the psychosocial impact of genetic testing for cardiomyopathies. Standardized psychological instruments including an adapted Multidimensional Impact of Cancer Risk Assessment (aMICRA), Impact of Event Scale (IES), and Satisfaction with Decision (SWD) scales were utilized. Patients with positive genetic test results had higher scores for intrusive thoughts, avoidance, and distress when compared to those with negative genetic test results and were also more likely to make or plan to make life changes because of the results of their genetic testing. Satisfaction with the decision to undergo genetic testing was similar regardless of genetic test results. The results of this study provide insight into the patient experience of genetic testing for cardiomyopathies and how these experiences are associated with genetic test results and cardiac history.
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- 2017
17. Novel candidate genes in esophageal atresia/tracheoesophageal fistula identified by exome sequencing
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Julie Khlevner, Jiayao Wang, Jianwen Que, Somaye Hashemifar, Priyanka Ahimaz, Yufeng Shen, William Middlesworth, Joseph A. Picoraro, Mahmoud Elfiky, and Wendy K. Chung
- Subjects
Proband ,Adult ,Male ,Mutation rate ,Candidate gene ,Adolescent ,rab3 GTP-Binding Proteins ,Tracheoesophageal fistula ,Biology ,Article ,Frameshift mutation ,03 medical and health sciences ,Gene Frequency ,Transcription Factors, TFIII ,Genetics ,medicine ,Missense mutation ,Humans ,Child ,Gene ,Esophageal Atresia ,Genetics (clinical) ,Exome sequencing ,Ribonucleoprotein, U5 Small Nuclear ,Adaptor Proteins, Signal Transducing ,0303 health sciences ,SOXB1 Transcription Factors ,Tumor Suppressor Proteins ,030305 genetics & heredity ,Infant ,Middle Aged ,medicine.disease ,Cadherins ,Peptide Elongation Factors ,Protocadherins ,Adaptor Proteins, Vesicular Transport ,Cytoskeletal Proteins ,Child, Preschool ,embryonic structures ,Mutation ,Female ,RNA Polymerase II ,Tracheoesophageal Fistula - Abstract
The various malformations of the aerodigestive tract collectively known as esophageal atresia/tracheoesophageal fistula (EA/TEF) constitute a rare group of birth defects of largely unknown etiology. Previous studies have identified a small number of rare genetic variants causing syndromes associated with EA/TEF. We performed a pilot exome sequencing study of 45 unrelated simplex trios (probands and parents) with EA/TEF. Thirteen had isolated and 32 had nonisolated EA/TEF; none had a family history of EA/TEF. We identified de novo variants in protein-coding regions, including 19 missense variants predicted to be deleterious (D-mis) and 3 likely gene-disrupting (LGD) variants. Consistent with previous studies of structural birth defects, there is a trend of increased burden of de novo D-mis in cases (1.57-fold increase over the background mutation rate), and the burden is greater in constrained genes (2.55-fold, p = 0.003). There is a frameshift de novo variant in EFTUD2, a known EA/TEF risk gene involved in mRNA splicing. Strikingly, 15 out of 19 de novo D-mis variants are located in genes that are putative target genes of EFTUD2 or SOX2 (another known EA/TEF gene), much greater than expected by chance (3.34-fold, p value = 7.20e−5). We estimated that 33% of patients can be attributed to de novo deleterious variants in known and novel genes. We identified APC2, AMER3, PCDH1, GTF3C1, POLR2B, RAB3GAP2, and ITSN1 as plausible candidate genes in the etiology of EA/TEF. We conclude that further genomic analysis to identify de novo variants will likely identify previously undescribed genetic causes of EA/TEF.
- Published
- 2019
18. Clinical genetic counselor experience in the new/expanded adoption of telehealth in the US and Canada during the COVID-19 pandemic
- Author
-
James Mirocha, Jessica Giordano, Pooja Mohan, Stephanie Cohen, Priyanka Ahimaz, Daria Ma, and Lola Cook
- Subjects
medicine.medical_specialty ,2019-20 coronavirus outbreak ,Coronavirus disease 2019 (COVID-19) ,business.industry ,Endocrinology, Diabetes and Metabolism ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Telehealth ,Biochemistry ,Endocrinology ,Family medicine ,Pandemic ,Genetics ,medicine ,Clinical genetic ,business ,Molecular Biology - Published
- 2021
19. Diagnostic exome sequencing in children: A survey of parental understanding, experience and psychological impact
- Author
-
Jimmy Duong, Ashley Wilson, Julia Wynn, R. Rabin, Josue Natanael Martinez, Robert L. Klitzman, Wendy K. Chung, U. Lichter‐Konecki, Alejandro Iglesias, M. Primiano, Megan T. Cho, Rachel Webster, Priyanka Ahimaz, Edwin Guzman, Kwame Anyane-Yeboa, C. Egan, Paul S. Appelbaum, E. Rosen, J.E. Shaw, Ruth Ottman, and R. Sisson
- Subjects
0301 basic medicine ,Adult ,Male ,Parents ,Genetic counseling ,Developmental Disabilities ,Genetic Counseling ,Disclosure ,030105 genetics & heredity ,Article ,law.invention ,03 medical and health sciences ,law ,Surveys and Questionnaires ,Exome Sequencing ,Genetics ,medicine ,Humans ,Exome ,Genetic Testing ,Child ,Genetics (clinical) ,Exome sequencing ,Depression (differential diagnoses) ,business.industry ,Regret ,Test (assessment) ,CLARITY ,Anxiety ,Female ,Personalized medicine ,medicine.symptom ,Psychology ,business ,Clinical psychology - Abstract
Clinical exome sequencing (CES) is increasingly being used as an effective diagnostic tool in the field of pediatric genetics. We sought to evaluate the parental experience, understanding and psychological impact of CES by conducting a survey study of English-speaking parents of children who had diagnostic CES. Parents of 192 unique patients participated. The parent's interpretation of the child's result agreed with the clinician's interpretation in 79% of cases, with more frequent discordance when the clinician's interpretation was uncertain. The majority (79%) reported no regret with the decision to have CES. Most (65%) reported complete satisfaction with the genetic counseling experience, and satisfaction was positively associated with years of genetic counselor (GC) experience. The psychological impact of CES was greatest for parents of children with positive results and for parents with anxiety or depression. The results of this study are important for helping clinicians to prepare families for the possible results and variable psychological impact of CES. The frequency of parental misinterpretation of test results indicates the need for additional clarity in the communication of results. Finally, while the majority of patients were satisfied with their genetic counseling, satisfaction was lower for new GCs, suggesting a need for targeted GC training for genomic testing.
- Published
- 2017
20. Sa2011 - Novel Candidate Genes in Esophageal Atresia/Tracheoesophageal Fistula Identified by Whole Exome Sequencing
- Author
-
Julie Khlevner, William Middlesworth, Jianwen Que, Joseph A. Picoraro, Wendy K. Chung, Mahmoud Elfiky, Priyanka Ahimaz, Yufeng Shen, and Jiayao Wang
- Subjects
Candidate gene ,Hepatology ,business.industry ,Gastroenterology ,Medicine ,Esophageal atresia/tracheoesophageal fistula ,Bioinformatics ,business ,Exome sequencing - Published
- 2018
21. De novo mutations in PURA are associated with hypotonia and developmental delay
- Author
-
Kwame Anyane-Yeboa, Jane Juusola, Monica Nardini, Priyanka Ahimaz, Kyle Retterer, Fran Kendall, Mislen Bauer, Wendy K. Chung, Beverly N. Hay, Megan T. Cho, Renkui Bai, Akemi J. Tanaka, Ashley Wilson, and Timothy J. Moss
- Subjects
Genetics ,Research Report ,Candidate gene ,Messenger RNA ,fungi ,Translation (biology) ,General Medicine ,Central hypotonia ,Microdeletion syndrome ,Biology ,generalized tonic seizures ,Phenotype ,Hypotonia ,medicine ,medicine.symptom ,central hypotonia ,severe global developmental delay ,De novo mutations ,generalized clonic seizures - Abstract
PURA is the leading candidate gene responsible for the developmental phenotype in the 5q31.3 microdeletion syndrome. De novo mutations in PURA were recently reported in 15 individuals with developmental features similar to the 5q31.3 microdeletion syndrome. Here we describe six unrelated children who were identified by clinical whole-exome sequencing (WES) to have novel de novo variants in PURA with a similar phenotype of hypotonia and developmental delay and frequently associated with seizures. The protein Purα (encoded by PURA) is involved in neuronal proliferation, dendrite maturation, and the transport of mRNA to translation sites during neuronal development. Mutations in PURA may alter normal brain development and impair neuronal function, leading to developmental delay and the seizures observed in patients with mutations in PURA.
- Published
- 2015
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