364 results on '"Roberts, Amy E."'
Search Results
2. The seventh international RASopathies symposium: Pathways to a cure—expanding knowledge, enhancing research, and therapeutic discovery
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Kontaridis, Maria I, Roberts, Amy E, Schill, Lisa, Schoyer, Lisa, Stronach, Beth, Andelfinger, Gregor, Aoki, Yoko, Axelrad, Marni E, Bakker, Annette, Bennett, Anton M, Broniscer, Alberto, Castel, Pau, Chang, Caitlin A, Cyganek, Lukas, Das, Tirtha K, Hertog, Jeroen, Galperin, Emilia, Garg, Shruti, Gelb, Bruce D, Gordon, Kristiana, Green, Tamar, Gripp, Karen W, Itkin, Maxim, Kiuru, Maija, Korf, Bruce R, Livingstone, Jeff R, López‐Juárez, Alejandro, Magoulas, Pilar L, Mansour, Sahar, Milner, Theresa, Parker, Elisabeth, Pierpont, Elizabeth I, Plouffe, Kevin, Rauen, Katherine A, Shankar, Suma P, Smith, Shane B, Stevenson, David A, Tartaglia, Marco, Van, Richard, Wagner, Morgan E, Ware, Stephanie M, and Zenker, Martin
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Pediatric ,Genetics ,Aetiology ,2.1 Biological and endogenous factors ,Good Health and Well Being ,Costello Syndrome ,Humans ,Mitogen-Activated Protein Kinases ,Noonan Syndrome ,Signal Transduction ,ras Proteins ,cardiofaciocutaneus syndrome ,Costello syndrome ,neurofibromatosis ,Noonan syndrome ,RASopathy ,signaling ,Clinical Sciences - Abstract
RASopathies are a group of genetic disorders that are caused by genes that affect the canonical Ras/mitogen-activated protein kinase (MAPK) signaling pathway. Despite tremendous progress in understanding the molecular consequences of these genetic anomalies, little movement has been made in translating these findings to the clinic. This year, the seventh International RASopathies Symposium focused on expanding the research knowledge that we have gained over the years to enhance new discoveries in the field, ones that we hope can lead to effective therapeutic treatments. Indeed, for the first time, research efforts are finally being translated to the clinic, with compassionate use of Ras/MAPK pathway inhibitors for the treatment of RASopathies. This biannual meeting, organized by the RASopathies Network, brought together basic scientists, clinicians, clinician scientists, patients, advocates, and their families, as well as representatives from pharmaceutical companies and the National Institutes of Health. A history of RASopathy gene discovery, identification of new disease genes, and the latest research, both at the bench and in the clinic, were discussed.
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- 2022
3. De novo variants in FRYL are associated with developmental delay, intellectual disability, and dysmorphic features
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Burrage, Lindsay C., Heaney, Jason D., Kim, Seon-Young, Lanza, Denise G., Liu, Zhandong, Mao, Dongxue, Milosavljevic, Aleksander, Nagamani, Sandesh C.S., Posey, Jennifer E., Ramamurthy, Uma, Ramanathan, Vivek, Rogers, Jeffrey, Rosenfeld, Jill A., Roth, Matthew, Zahedi Darshoori, Ramin, Pan, Xueyang, Tao, Alice M., Lu, Shenzhao, Ma, Mengqi, Hannan, Shabab B., Slaugh, Rachel, Drewes Williams, Sarah, O'Grady, Lauren, Kanca, Oguz, Person, Richard, Carter, Melissa T., Platzer, Konrad, Schnabel, Franziska, Abou Jamra, Rami, Roberts, Amy E., Newburger, Jane W., Revah-Politi, Anya, Granadillo, Jorge L., Stegmann, Alexander P.A., Sinnema, Margje, Accogli, Andrea, Salpietro, Vincenzo, Capra, Valeria, Ghaloul-Gonzalez, Lina, Brueckner, Martina, Simon, Marleen E.H., Sweetser, David A., Glinton, Kevin E., Kirk, Susan E., Wangler, Michael F., Yamamoto, Shinya, Chung, Wendy K., and Bellen, Hugo J.
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- 2024
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4. Contributors
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Abrams, Dominic J., primary, Alexander, Mark E., additional, Alexander, Peta M.A., additional, Allan, Catherine, additional, Baird, Christopher W., additional, Bergersen, Lisa, additional, Beroukhim, Rebecca, additional, Bevilacqua, Laura M., additional, Bezzerides, Vassilios, additional, Blume, Elizabeth D., additional, Breitbart, Roger E., additional, Brown, David W., additional, Callahan, Ryan, additional, Carreon, Chrystalle Katte, additional, Castellanos, Daniel A., additional, Chen, Ming Hui, additional, Cheng, Henry, additional, Colan, Steven D., additional, Daly, Kevin P., additional, de Ferranti, Sarah D., additional, del Nido, Pedro J., additional, DeWitt, Elizabeth, additional, DiNardo, James, additional, Dionne, Audrey, additional, Emani, Sitaram M., additional, Esch, Jesse J., additional, Esteso, Paul, additional, Feins, Eric N., additional, Freed, Michael D., additional, Friedman, Kevin, additional, Fulton, David R., additional, Fynn-Thompson, Francis, additional, Garbern, Jessica C., additional, Garcia-Mancebo, Julia, additional, Gauthier, Naomi, additional, Geggel, Robert L., additional, Geisser, Diana L., additional, Gellis, Laura, additional, Geva, Tal, additional, Ghbeis, Muhammad Bakr, additional, Ghelani, Sunil J., additional, Goldberg, Sarah W., additional, Gurvitz, Michelle, additional, Hames, Daniel L., additional, Harrild, David M., additional, Hartz, Jacob, additional, Hickey, Patricia, additional, Hoganson, David, additional, Jenkins, Kathy, additional, Kane, David, additional, Kaza, Aditya K., additional, Kheir, John N., additional, Kumar, R. Krishna, additional, Kwon, Michael H., additional, Lacro, Ronald V., additional, Landzberg, Michael J., additional, Lang, Peter, additional, LaRovere, Joan M., additional, Levine, Jami, additional, Lock, James Ernest, additional, Lyon, Shannon, additional, Mah, Douglas Y., additional, Marx, Gerald R., additional, Maschietto, Nicola, additional, Matte, Gregory S., additional, Mayer, John E., additional, Mills, Kimberly I., additional, Mistry, Kshitij, additional, Mullen, Mary P., additional, Nasr, Viviane G., additional, Nathan, Meena, additional, Newburger, Jane W., additional, O’Brien, Patricia, additional, O’Brien, Sharon E., additional, O’Leary, Edward T., additional, Porras, Diego, additional, Powell, Andrew J., additional, Prakash, Ashwin, additional, Pu, William T., additional, Quiat, Daniel, additional, Quinn, Brian, additional, Quinonez, Luis, additional, Rathod, Rahul H., additional, Rhodes, Jonathan, additional, Roberts, Amy E., additional, Rodriguez-Monserrate, Carla P., additional, Ronai, Christina, additional, Saia, Theresa, additional, Saleeb, Susan F., additional, Salvin, Joshua W., additional, Sanders, Stephen P., additional, Schidlow, David, additional, Shafer, Keri M., additional, Siegel, Bryan D., additional, Singh, Michael N., additional, Singh, Tajinder, additional, Teele, Sarah A., additional, Thiagarajan, Ravi R., additional, Triedman, John K., additional, Tworetzky, Wayne, additional, Valente, Anne Marie, additional, VanderPluym, Christina, additional, Walsh, Edward P., additional, Wu, Fred Ming-Chieh, additional, and Yin, Suellen, additional
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- 2025
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5. Genetics of congenital heart disease
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Roberts, Amy E., primary and Lacro, Ronald V., additional
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- 2025
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6. Dysmorphology and syndromes
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Lacro, Ronald V., primary and Roberts, Amy E., additional
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- 2025
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7. Abstract 17273: Phenotypic Clustering of Patients With Heterotaxy Syndrome Predicts Outcomes of Mortality and Transplantation
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Bucholz, Emily M, Sompolinsky, Tehila, Beroukhim, Rebecca S, Castellanos, Daniel A, Dewitt, Elizabeth S, Geva, Tal, Ghelani, Sunil J, Hoganson, David, Marx, Gerald R, Roberts, Amy E, Teele, Sarah A, and Schidlow, David N
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- 2023
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8. Sengers syndrome and AGK-related disorders - Minireview of phenotypic variability and clinical outcomes in molecularly confirmed cases
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Wu, Chen-Han Wilfred, Caha, Martin, Smoot, Leslie, Harris, David J., Roberts, Amy E., Sacharow, Stephanie, and Bodamer, Olaf
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- 2023
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9. De novo Damaging Variants, Clinical Phenotypes and Post-Operative Outcomes in Congenital Heart Disease
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Boskovski, Marko T, Homsy, Jason, Nathan, Meena, Sleeper, Lynn A, Morton, Sarah, Manheimer, Kathryn B, Tai, Angela, Gorham, Joshua, Lewis, Matthew, Swartz, Michael, Alfieris, George M, Bacha, Emile A, Karimi, Mohsen, Meyer, David, Nguyen, Khanh, Bernstein, Daniel, Romano-Adesman, Angela, Porter, George A, Goldmuntz, Elizabeth, Chung, Wendy K, Srivastava, Deepak, Kaltman, Jonathan R, Tristani-Firouzi, Martin, Lifton, Richard, Roberts, Amy E, Gaynor, J William, Gelb, Bruce D, Kim, Richard, Seidman, Jonathan G, Brueckner, Martina, Mayer, John E, Newburger, Jane W, and Seidman, Christine E
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Biomedical and Clinical Sciences ,Cardiovascular Medicine and Haematology ,Clinical Sciences ,Genetics ,Patient Safety ,Congenital Structural Anomalies ,Clinical Research ,Human Genome ,Transplantation ,Heart Disease ,Cardiovascular ,Pediatric ,Aetiology ,2.1 Biological and endogenous factors ,Good Health and Well Being ,Adolescent ,Child ,Child ,Preschool ,Chromosomes ,Human ,Pair 15 ,Chromosomes ,Human ,Pair 3 ,DNA Copy Number Variations ,Female ,Heart Defects ,Congenital ,Heart Transplantation ,Humans ,Infant ,Kaplan-Meier Estimate ,Machine Learning ,Male ,Odds Ratio ,Phenotype ,Proportional Hazards Models ,Exome Sequencing ,genomics ,congenital heart disease ,heart transplantation ,mortality ,survival ,Medical Biotechnology ,Cardiorespiratory Medicine and Haematology ,Cardiovascular System & Hematology ,Cardiovascular medicine and haematology - Abstract
BackgroundDe novo genic and copy number variants are enriched in patients with congenital heart disease, particularly those with extra-cardiac anomalies. The impact of de novo damaging variants on outcomes following cardiac repair is unknown.MethodsWe studied 2517 patients with congenital heart disease who had undergone whole-exome sequencing as part of the CHD GENES study (Congenital Heart Disease Genetic Network).ResultsTwo hundred ninety-four patients (11.7%) had clinically significant de novo variants. Patients with de novo damaging variants were 2.4 times more likely to have extra-cardiac anomalies (P=5.63×10-12). In 1268 patients (50.4%) who had surgical data available and underwent open-heart surgery exclusive of heart transplantation as their first operation, we analyzed transplant-free survival following the first operation. Median follow-up was 2.65 years. De novo variants were associated with worse transplant-free survival (hazard ratio, 3.51; P=5.33×10-04) and longer times to final extubation (hazard ratio, 0.74; P=0.005). As de novo variants had a significant interaction with extra-cardiac anomalies for transplant-free survival (P=0.003), de novo variants conveyed no additional risk for transplant-free survival for patients with these anomalies (adjusted hazard ratio, 1.96; P=0.06). By contrast, de novo variants in patients without extra-cardiac anomalies were associated with worse transplant-free survival during follow-up (hazard ratio, 11.21; P=1.61×10-05) than that of patients with no de novo variants. Using agnostic machine-learning algorithms, we identified de novo copy number variants at 15q25.2 and 15q11.2 as being associated with worse transplant-free survival and 15q25.2, 22q11.21, and 3p25.2 as being associated with prolonged time to final extubation.ConclusionsIn patients with congenital heart disease undergoing open-heart surgery, de novo variants were associated with worse transplant-free survival and longer times on the ventilator. De novo variants were most strongly associated with adverse outcomes among patients without extra-cardiac anomalies, suggesting a benefit for preoperative genetic testing even when genetic abnormalities are not suspected during routine clinical practice. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01196182.
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- 2020
10. Systems Analysis Implicates WAVE2 Complex in the Pathogenesis of Developmental Left-Sided Obstructive Heart Defects.
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Edwards, Jonathan J, Rouillard, Andrew D, Fernandez, Nicolas F, Wang, Zichen, Lachmann, Alexander, Shankaran, Sunita S, Bisgrove, Brent W, Demarest, Bradley, Turan, Nahid, Srivastava, Deepak, Bernstein, Daniel, Deanfield, John, Giardini, Alessandro, Porter, George, Kim, Richard, Roberts, Amy E, Newburger, Jane W, Goldmuntz, Elizabeth, Brueckner, Martina, Lifton, Richard P, Seidman, Christine E, Chung, Wendy K, Tristani-Firouzi, Martin, Yost, H Joseph, Ma'ayan, Avi, and Gelb, Bruce D
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CHD ,congenital heart disease ,CORUM ,Comprehensive Resource of Mammalian Protein Complexes ,CRISPR ,clustered regularly interspaced short palindromic repeats ,CTD ,conotruncal defect ,GOBP ,Gene Ontology biological processes ,HHE ,high heart expression ,HLHS ,hypoplastic left heart syndrome ,HTX ,heterotaxy ,LVOTO ,left ventricular outflow tract obstruction ,MGI ,Mouse Genome Informatics ,PCGC ,Pediatric Cardiac Genomics Consortium ,PPI ,protein-protein interaction ,congenital heart disease ,systems biology ,translational genomics ,CHD ,CORUM ,Comprehensive Resource of Mammalian Protein Complexes ,CRISPR ,clustered regularly interspaced short palindromic repeats ,CTD ,conotruncal defect ,GOBP ,Gene Ontology biological processes ,HHE ,high heart expression ,HLHS ,hypoplastic left heart syndrome ,HTX ,heterotaxy ,LVOTO ,left ventricular outflow tract obstruction ,MGI ,Mouse Genome Informatics ,PCGC ,Pediatric Cardiac Genomics Consortium ,PPI ,protein-protein interaction ,Cardiorespiratory Medicine and Haematology ,Clinical Sciences - Abstract
Genetic variants are the primary driver of congenital heart disease (CHD) pathogenesis. However, our ability to identify causative variants is limited. To identify causal CHD genes that are associated with specific molecular functions, the study used prior knowledge to filter de novo variants from 2,881 probands with sporadic severe CHD. This approach enabled the authors to identify an association between left ventricular outflow tract obstruction lesions and genes associated with the WAVE2 complex and regulation of small GTPase-mediated signal transduction. Using CRISPR zebrafish knockdowns, the study confirmed that WAVE2 complex proteins brk1, nckap1, and wasf2 and the regulators of small GTPase signaling cul3a and racgap1 are critical to cardiac development.
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- 2020
11. Meta-regression of sulcal patterns, clinical and environmental factors on neurodevelopmental outcomes in participants with multiple CHD types
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Maleyeff, Lara, primary, Park, Hannah J, additional, Khazal, Zahra S H, additional, Wypij, David, additional, Rollins, Caitlin K, additional, Yun, Hyuk Jin, additional, Bellinger, David C, additional, Watson, Christopher G, additional, Roberts, Amy E, additional, Newburger, Jane W, additional, Grant, P Ellen, additional, Im, Kiho, additional, and Morton, Sarah U, additional
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- 2024
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12. Hypertrophic Cardiomyopathy in RASopathies: Diagnosis, Clinical Characteristics, Prognostic Implications, and Management
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Lioncino, Michele, Monda, Emanuele, Verrillo, Federica, Moscarella, Elisabetta, Calcagni, Giulio, Drago, Fabrizio, Marino, Bruno, Digilio, Maria Cristina, Putotto, Carolina, Calabrò, Paolo, Russo, Maria Giovanna, Roberts, Amy E., Gelb, Bruce D., Tartaglia, Marco, and Limongelli, Giuseppe
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- 2022
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13. Contribution of rare inherited and de novo variants in 2,871 congenital heart disease probands
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Jin, Sheng Chih, Homsy, Jason, Zaidi, Samir, Lu, Qiongshi, Morton, Sarah, DePalma, Steven R, Zeng, Xue, Qi, Hongjian, Chang, Weni, Sierant, Michael C, Hung, Wei-Chien, Haider, Shozeb, Zhang, Junhui, Knight, James, Bjornson, Robert D, Castaldi, Christopher, Tikhonoa, Irina R, Bilguvar, Kaya, Mane, Shrikant M, Sanders, Stephan J, Mital, Seema, Russell, Mark W, Gaynor, J William, Deanfield, John, Giardini, Alessandro, Porter, George A, Srivastava, Deepak, Lo, Cecelia W, Shen, Yufeng, Watkins, W Scott, Yandell, Mark, Yost, H Joseph, Tristani-Firouzi, Martin, Newburger, Jane W, Roberts, Amy E, Kim, Richard, Zhao, Hongyu, Kaltman, Jonathan R, Goldmuntz, Elizabeth, Chung, Wendy K, Seidman, Jonathan G, Gelb, Bruce D, Seidman, Christine E, Lifton, Richard P, and Brueckner, Martina
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Biological Sciences ,Genetics ,Cardiovascular ,Pediatric ,Congenital Structural Anomalies ,Brain Disorders ,Heart Disease ,Heart Disease - Coronary Heart Disease ,2.1 Biological and endogenous factors ,Aetiology ,Adult ,Autistic Disorder ,Cardiac Myosins ,Case-Control Studies ,Child ,Exome ,Female ,Gene Expression ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Growth Differentiation Factor 1 ,Heart Defects ,Congenital ,Heterozygote ,High-Throughput Nucleotide Sequencing ,Homozygote ,Humans ,Male ,Mutation ,Myosin Heavy Chains ,Pedigree ,Risk ,Vascular Endothelial Growth Factor Receptor-3 ,Medical and Health Sciences ,Developmental Biology ,Agricultural biotechnology ,Bioinformatics and computational biology - Abstract
Congenital heart disease (CHD) is the leading cause of mortality from birth defects. Here, exome sequencing of a single cohort of 2,871 CHD probands, including 2,645 parent-offspring trios, implicated rare inherited mutations in 1.8%, including a recessive founder mutation in GDF1 accounting for ∼5% of severe CHD in Ashkenazim, recessive genotypes in MYH6 accounting for ∼11% of Shone complex, and dominant FLT4 mutations accounting for 2.3% of Tetralogy of Fallot. De novo mutations (DNMs) accounted for 8% of cases, including ∼3% of isolated CHD patients and ∼28% with both neurodevelopmental and extra-cardiac congenital anomalies. Seven genes surpassed thresholds for genome-wide significance, and 12 genes not previously implicated in CHD had >70% probability of being disease related. DNMs in ∼440 genes were inferred to contribute to CHD. Striking overlap between genes with damaging DNMs in probands with CHD and autism was also found.
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- 2017
14. Genome-Wide Association Study to Find Modifiers for Tetralogy of Fallot in the 22q11.2 Deletion Syndrome Identifies Variants in the GPR98 Locus on 5q14.3
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Guo, Tingwei, Repetto, Gabriela M, McDonald McGinn, Donna M, Chung, Jonathan H, Nomaru, Hiroko, Campbell, Christopher L, Blonska, Anna, Bassett, Anne S, Chow, Eva WC, Mlynarski, Elisabeth E, Swillen, Ann, Vermeesch, Joris, Devriendt, Koen, Gothelf, Doron, Carmel, Miri, Michaelovsky, Elena, Schneider, Maude, Eliez, Stephan, Antonarakis, Stylianos E, Coleman, Karlene, Tomita-Mitchell, Aoy, Mitchell, Michael E, Digilio, M Cristina, Dallapiccola, Bruno, Marino, Bruno, Philip, Nicole, Busa, Tiffany, Kushan-Wells, Leila, Bearden, Carrie E, Piotrowicz, Małgorzata, Hawuła, Wanda, Roberts, Amy E, Tassone, Flora, Simon, Tony J, van Duin, Esther DA, van Amelsvoort, Thérèse A, Kates, Wendy R, Zackai, Elaine, Johnston, H Richard, Cutler, David J, Agopian, AJ, Goldmuntz, Elizabeth, Mitchell, Laura E, Wang, Tao, Emanuel, Beverly S, and Morrow, Bernice E
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Biomedical and Clinical Sciences ,Cardiovascular Medicine and Haematology ,Genetics ,Rare Diseases ,Congenital Structural Anomalies ,Clinical Research ,Human Genome ,Heart Disease ,Cardiovascular ,Pediatric ,2.1 Biological and endogenous factors ,Aetiology ,Congenital ,Chromatin ,Chromosomes ,Human ,Pair 5 ,DiGeorge Syndrome ,Genetic Loci ,Genome-Wide Association Study ,Genotype ,High-Throughput Nucleotide Sequencing ,Humans ,Linkage Disequilibrium ,MEF2 Transcription Factors ,Oligonucleotide Array Sequence Analysis ,Phenotype ,Polymorphism ,Single Nucleotide ,Receptors ,G-Protein-Coupled ,Sequence Analysis ,DNA ,Tetralogy of Fallot ,chromosomes ,DiGeorge syndrome ,genotype ,ivelo-cardio-facial syndrome ,tetralogy of Fallot ,International 22q11.2 Consortium/Brain and Behavior Consortium* ,Medical Biotechnology ,Cardiorespiratory Medicine and Haematology ,Cardiovascular System & Hematology ,Cardiovascular medicine and haematology - Abstract
The 22q11.2 deletion syndrome (22q11.2DS; DiGeorge syndrome/velocardiofacial syndrome) occurs in 1 of 4000 live births, and 60% to 70% of affected individuals have congenital heart disease, ranging from mild to severe. In our cohort of 1472 subjects with 22q11.2DS, a total of 62% (n=906) have congenital heart disease and 36% (n=326) of these have tetralogy of Fallot (TOF), comprising the largest subset of severe congenital heart disease in the cohort. To identify common genetic variants associated with TOF in individuals with 22q11.2DS, we performed a genome-wide association study using Affymetrix 6.0 array and imputed genotype data. In our cohort, TOF was significantly associated with a genotyped single-nucleotide polymorphism (rs12519770, P=2.98×10-8) in an intron of the adhesion GPR98 (G-protein-coupled receptor V1) gene on chromosome 5q14.3. There was also suggestive evidence of association between TOF and several additional single-nucleotide polymorphisms in this region. Some genome-wide significant loci in introns or noncoding regions could affect regulation of genes nearby or at a distance. On the basis of this possibility, we examined existing Hi-C chromatin conformation data to identify genes that might be under shared transcriptional regulation within the region on 5q14.3. There are 6 genes in a topologically associated domain of chromatin with GPR98, including MEF2C (Myocyte-specific enhancer factor 2C). MEF2C is the only gene that is known to affect heart development in mammals and might be of interest with respect to 22q11.2DS. In conclusion, common variants may contribute to TOF in 22q11.2DS and may function in cardiac outflow tract development.
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- 2017
15. De novo variants in FRYL are associated with developmental delay, intellectual disability, and dysmorphic features
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Pan, Xueyang, primary, Tao, Alice M., additional, Lu, Shenzhao, additional, Ma, Mengqi, additional, Hannan, Shabab B., additional, Slaugh, Rachel, additional, Drewes Williams, Sarah, additional, O'Grady, Lauren, additional, Kanca, Oguz, additional, Person, Richard, additional, Carter, Melissa T., additional, Platzer, Konrad, additional, Schnabel, Franziska, additional, Abou Jamra, Rami, additional, Roberts, Amy E., additional, Newburger, Jane W., additional, Revah-Politi, Anya, additional, Granadillo, Jorge L., additional, Stegmann, Alexander P.A., additional, Sinnema, Margje, additional, Accogli, Andrea, additional, Salpietro, Vincenzo, additional, Capra, Valeria, additional, Ghaloul-Gonzalez, Lina, additional, Brueckner, Martina, additional, Simon, Marleen E.H., additional, Sweetser, David A., additional, Glinton, Kevin E., additional, Kirk, Susan E., additional, Wangler, Michael F., additional, Yamamoto, Shinya, additional, Chung, Wendy K., additional, Bellen, Hugo J., additional, Burrage, Lindsay C., additional, Heaney, Jason D., additional, Kim, Seon-Young, additional, Lanza, Denise G., additional, Liu, Zhandong, additional, Mao, Dongxue, additional, Milosavljevic, Aleksander, additional, Nagamani, Sandesh C.S., additional, Posey, Jennifer E., additional, Ramamurthy, Uma, additional, Ramanathan, Vivek, additional, Rogers, Jeffrey, additional, Rosenfeld, Jill A., additional, Roth, Matthew, additional, and Zahedi Darshoori, Ramin, additional
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- 2024
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16. Matrisome and Immune Pathways Contribute to Extreme Vascular Outcomes in Williams–Beuren Syndrome
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Liu, Delong, primary, Billington, Charles J., additional, Raja, Neelam, additional, Wong, Zoe C., additional, Levin, Mark D., additional, Resch, Wulfgang, additional, Alba, Camille, additional, Hupalo, Daniel N., additional, Biamino, Elisa, additional, Bedeschi, Maria Francesca, additional, Digilio, Maria Cristina, additional, Squeo, Gabriella Maria, additional, Villa, Roberta, additional, Parrish, Pheobe C. R., additional, Knutsen, Russell H., additional, Osgood, Sharon, additional, Freeman, Joy A., additional, Dalgard, Clifton L., additional, Merla, Giuseppe, additional, Pober, Barbara R., additional, Mervis, Carolyn B., additional, Roberts, Amy E., additional, Morris, Colleen A., additional, Osborne, Lucy R., additional, and Kozel, Beth A., additional
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- 2024
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17. Abstract 15551: Pulmonary Hypertension in Patients With Noonan Syndrome Undergoing Cardiac Catheterization
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Collins, Shane, Critser, Paul, Gauvreau, Kimberlee, Roberts, Amy E, and Mullen, Mary P
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- 2022
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18. The Evolving Role of Genetic Evaluation in the Prenatal Diagnosis and Management of Congenital Heart Disease.
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Bucholz, Emily M., Morton, Sarah U., Madriago, Erin, Roberts, Amy E., and Ronai, Christina
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- 2024
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19. Rare copy number variants and congenital heart defects in the 22q11.2 deletion syndrome.
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Mlynarski, Elisabeth E, Xie, Michael, Taylor, Deanne, Sheridan, Molly B, Guo, Tingwei, Racedo, Silvia E, McDonald-McGinn, Donna M, Chow, Eva WC, Vorstman, Jacob, Swillen, Ann, Devriendt, Koen, Breckpot, Jeroen, Digilio, Maria Cristina, Marino, Bruno, Dallapiccola, Bruno, Philip, Nicole, Simon, Tony J, Roberts, Amy E, Piotrowicz, Małgorzata, Bearden, Carrie E, Eliez, Stephan, Gothelf, Doron, Coleman, Karlene, Kates, Wendy R, Devoto, Marcella, Zackai, Elaine, Heine-Suñer, Damian, Goldmuntz, Elizabeth, Bassett, Anne S, Morrow, Bernice E, Emanuel, Beverly S, and International Chromosome 22q11.2 Consortium
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International Chromosome 22q11.2 Consortium ,Chromosomes ,Human ,Pair 22 ,Humans ,Heart Defects ,Congenital ,DiGeorge Syndrome ,Chromosome Deletion ,DNA Copy Number Variations ,Genotyping Techniques ,Human Genome ,Rare Diseases ,Heart Disease ,Cardiovascular ,Pediatric ,Clinical Research ,Prevention ,Genetics ,Congenital Structural Anomalies ,2.1 Biological and endogenous factors ,Congenital ,Genetics & Heredity ,Complementary and Alternative Medicine ,Paediatrics and Reproductive Medicine - Abstract
The 22q11.2 deletion syndrome (22q11DS; velocardiofacial/DiGeorge syndrome; VCFS/DGS; MIM #192430; 188400) is the most common microdeletion syndrome. The phenotypic presentation of 22q11DS is highly variable; approximately 60-75 % of 22q11DS patients have been reported to have a congenital heart defect (CHD), mostly of the conotruncal type, and/or aortic arch defect. The etiology of the cardiac phenotypic variability is not currently known for the majority of patients. We hypothesized that rare copy number variants (CNVs) outside the 22q11.2 deleted region may modify the risk of being born with a CHD in this sensitized population. Rare CNV analysis was performed using Affymetrix SNP Array 6.0 data from 946 22q11DS subjects with CHDs (n = 607) or with normal cardiac anatomy (n = 339). Although there was no significant difference in the overall burden of rare CNVs, an overabundance of CNVs affecting cardiac-related genes was detected in 22q11DS individuals with CHDs. When the rare CNVs were examined with regard to gene interactions, specific cardiac networks, such as Wnt signaling, appear to be overrepresented in 22q11DS CHD cases but not 22q11DS controls with a normal heart. Collectively, these data suggest that CNVs outside the 22q11.2 region may contain genes that modify risk for CHDs in some 22q11DS patients.
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- 2016
20. Association of genetic and sulcal traits with executive function in congenital heart disease
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Maleyeff, Lara, primary, Newburger, Jane W., additional, Wypij, David, additional, Thomas, Nina H., additional, Anagnoustou, Evdokia, additional, Brueckner, Martina, additional, Chung, Wendy K., additional, Cleveland, John, additional, Cunningham, Sean, additional, Gelb, Bruce D., additional, Goldmuntz, Elizabeth, additional, Hagler, Donald J, additional, Huang, Hao, additional, King, Eileen, additional, McQuillen, Patrick, additional, Miller, Thomas A., additional, Norris‐Brilliant, Ami, additional, Porter, George A., additional, Roberts, Amy E., additional, Grant, P. Ellen, additional, Im, Kiho, additional, and Morton, Sarah U., additional
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- 2023
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21. Epilepsy in cardiofaciocutaneous syndrome: Clinical burden and response to anti‐seizure medication
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Kenney‐Jung, Daniel L., primary, Collazo‐Lopez, Josue E., additional, Rogers, Dante J., additional, Shanley, Ryan, additional, Zatkalik, Abigail L., additional, Whitmarsh, Ashley E., additional, Roberts, Amy E., additional, Zenker, Martin, additional, and Pierpont, Elizabeth I., additional
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- 2023
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22. De novo mutations in congenital heart disease with neurodevelopmental and other congenital anomalies
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Homsy, Jason, Zaidi, Samir, Shen, Yufeng, Ware, James S, Samocha, Kaitlin E, Karczewski, Konrad J, DePalma, Steven R, McKean, David, Wakimoto, Hiroko, Gorham, Josh, Jin, Sheng Chih, Deanfield, John, Giardini, Alessandro, Porter, George A, Kim, Richard, Bilguvar, Kaya, López-Giráldez, Francesc, Tikhonova, Irina, Mane, Shrikant, Romano-Adesman, Angela, Qi, Hongjian, Vardarajan, Badri, Ma, Lijiang, Daly, Mark, Roberts, Amy E, Russell, Mark W, Mital, Seema, Newburger, Jane W, Gaynor, J William, Breitbart, Roger E, Iossifov, Ivan, Ronemus, Michael, Sanders, Stephan J, Kaltman, Jonathan R, Seidman, Jonathan G, Brueckner, Martina, Gelb, Bruce D, Goldmuntz, Elizabeth, Lifton, Richard P, Seidman, Christine E, and Chung, Wendy K
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Congenital Structural Anomalies ,Genetics ,Pediatric ,Heart Disease ,Cardiovascular ,Brain ,Child ,Congenital Abnormalities ,Exome ,Heart Defects ,Congenital ,Humans ,Mutation ,Nervous System Malformations ,Neurogenesis ,Prognosis ,RNA Splicing ,RNA Splicing Factors ,RNA ,Messenger ,RNA-Binding Proteins ,Repressor Proteins ,Transcription ,Genetic ,General Science & Technology - Abstract
Congenital heart disease (CHD) patients have an increased prevalence of extracardiac congenital anomalies (CAs) and risk of neurodevelopmental disabilities (NDDs). Exome sequencing of 1213 CHD parent-offspring trios identified an excess of protein-damaging de novo mutations, especially in genes highly expressed in the developing heart and brain. These mutations accounted for 20% of patients with CHD, NDD, and CA but only 2% of patients with isolated CHD. Mutations altered genes involved in morphogenesis, chromatin modification, and transcriptional regulation, including multiple mutations in RBFOX2, a regulator of mRNA splicing. Genes mutated in other cohorts examined for NDD were enriched in CHD cases, particularly those with coexisting NDD. These findings reveal shared genetic contributions to CHD, NDD, and CA and provide opportunities for improved prognostic assessment and early therapeutic intervention in CHD patients.
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- 2015
23. Copy-Number Variation of the Glucose Transporter Gene SLC2A3 and Congenital Heart Defects in the 22q11.2 Deletion Syndrome
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Mlynarski, Elisabeth E, Sheridan, Molly B, Xie, Michael, Guo, Tingwei, Racedo, Silvia E, McDonald-McGinn, Donna M, Gai, Xiaowu, Chow, Eva WC, Vorstman, Jacob, Swillen, Ann, Devriendt, Koen, Breckpot, Jeroen, Digilio, Maria Cristina, Marino, Bruno, Dallapiccola, Bruno, Philip, Nicole, Simon, Tony J, Roberts, Amy E, Piotrowicz, Małgorzata, Bearden, Carrie E, Eliez, Stephan, Gothelf, Doron, Coleman, Karlene, Kates, Wendy R, Devoto, Marcella, Zackai, Elaine, Heine-Suñer, Damian, Shaikh, Tamim H, Bassett, Anne S, Goldmuntz, Elizabeth, Morrow, Bernice E, Emanuel, Beverly S, and Consortium, the International Chromosome 22q11 2
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Biomedical and Clinical Sciences ,Cardiovascular Medicine and Haematology ,Rare Diseases ,Congenital Structural Anomalies ,Genetics ,Heart Disease ,Clinical Research ,Cardiovascular ,Prevention ,Pediatric ,Aetiology ,2.1 Biological and endogenous factors ,Adult ,Aorta ,Thoracic ,DNA Copy Number Variations ,DiGeorge Syndrome ,Female ,Genotype ,Glucose Transporter Type 3 ,Heart Defects ,Congenital ,Humans ,Male ,Polymorphism ,Single Nucleotide ,International Chromosome 22q11.2 Consortium ,Biological Sciences ,Medical and Health Sciences ,Genetics & Heredity ,Biological sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
The 22q11.2 deletion syndrome (22q11DS; velocardiofacial/DiGeorge syndrome; VCFS/DGS) is the most common microdeletion syndrome and the phenotypic presentation is highly variable. Approximately 65% of individuals with 22q11DS have a congenital heart defect (CHD), mostly of the conotruncal type, and/or an aortic arch defect. The etiology of this phenotypic variability is not currently known. We hypothesized that copy-number variants (CNVs) outside the 22q11.2 deleted region might increase the risk of being born with a CHD in this sensitized population. Genotyping with Affymetrix SNP Array 6.0 was performed on two groups of subjects with 22q11DS separated by time of ascertainment and processing. CNV analysis was completed on a total of 949 subjects (cohort 1, n = 562; cohort 2, n = 387), 603 with CHDs (cohort 1, n = 363; cohort 2, n = 240) and 346 with normal cardiac anatomy (cohort 1, n = 199; cohort 2, n = 147). Our analysis revealed that a duplication of SLC2A3 was the most frequent CNV identified in the first cohort. It was present in 18 subjects with CHDs and 1 subject without (p = 3.12 × 10(-3), two-tailed Fisher's exact test). In the second cohort, the SLC2A3 duplication was also significantly enriched in subjects with CHDs (p = 3.30 × 10(-2), two-tailed Fisher's exact test). The SLC2A3 duplication was the most frequent CNV detected and the only significant finding in our combined analysis (p = 2.68 × 10(-4), two-tailed Fisher's exact test), indicating that the SLC2A3 duplication might serve as a genetic modifier of CHDs and/or aortic arch anomalies in individuals with 22q11DS.
- Published
- 2015
24. MATR3 disruption in human and mouse associated with bicuspid aortic valve, aortic coarctation and patent ductus arteriosus
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Quintero-Rivera, Fabiola, Xi, Qiongchao J, Keppler-Noreuil, Kim M, Lee, Ji Hyun, Higgins, Anne W, Anchan, Raymond M, Roberts, Amy E, Seong, Ihn Sik, Fan, Xueping, Lage, Kasper, Lu, Lily Y, Tao, Joanna, Hu, Xuchen, Berezney, Ronald, Gelb, Bruce D, Kamp, Anna, Moskowitz, Ivan P, Lacro, Ronald V, Lu, Weining, Morton, Cynthia C, Gusella, James F, and Maas, Richard L
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Cardiovascular ,Heart Disease ,Congenital Structural Anomalies ,Pediatric ,Genetics ,2.1 Biological and endogenous factors ,Aetiology ,Adolescent ,Animals ,Aortic Coarctation ,Aortic Valve ,Bicuspid Aortic Valve Disease ,Child ,Preschool ,DNA-Binding Proteins ,Ductus Arteriosus ,Patent ,Female ,Gene Silencing ,Heart Valve Diseases ,Heart Ventricles ,Humans ,Infant ,Newborn ,Male ,Mice ,Mutagenesis ,Insertional ,Nuclear Matrix-Associated Proteins ,RNA-Binding Proteins ,Translocation ,Genetic ,Biological Sciences ,Medical and Health Sciences ,Genetics & Heredity - Abstract
Cardiac left ventricular outflow tract (LVOT) defects represent a common but heterogeneous subset of congenital heart disease for which gene identification has been difficult. We describe a 46,XY,t(1;5)(p36.11;q31.2)dn translocation carrier with pervasive developmental delay who also exhibited LVOT defects, including bicuspid aortic valve (BAV), coarctation of the aorta (CoA) and patent ductus arteriosus (PDA). The 1p breakpoint disrupts the 5' UTR of AHDC1, which encodes AT-hook DNA-binding motif containing-1 protein, and AHDC1-truncating mutations have recently been described in a syndrome that includes developmental delay, but not congenital heart disease [Xia, F., Bainbridge, M.N., Tan, T.Y., Wangler, M.F., Scheuerle, A.E., Zackai, E.H., Harr, M.H., Sutton, V.R., Nalam, R.L., Zhu, W. et al. (2014) De Novo truncating mutations in AHDC1 in individuals with syndromic expressive language delay, hypotonia, and sleep apnea. Am. J. Hum. Genet., 94, 784-789]. On the other hand, the 5q translocation breakpoint disrupts the 3' UTR of MATR3, which encodes the nuclear matrix protein Matrin 3, and mouse Matr3 is strongly expressed in neural crest, developing heart and great vessels, whereas Ahdc1 is not. To further establish MATR3 3' UTR disruption as the cause of the proband's LVOT defects, we prepared a mouse Matr3(Gt-ex13) gene trap allele that disrupted the 3' portion of the gene. Matr3(Gt-ex13) homozygotes are early embryo lethal, but Matr3(Gt-ex13) heterozygotes exhibit incompletely penetrant BAV, CoA and PDA phenotypes similar to those in the human proband, as well as ventricular septal defect (VSD) and double-outlet right ventricle (DORV). Both the human MATR3 translocation breakpoint and the mouse Matr3(Gt-ex13) gene trap insertion disturb the polyadenylation of MATR3 transcripts and alter Matrin 3 protein expression, quantitatively or qualitatively. Thus, subtle perturbations in Matrin 3 expression appear to cause similar LVOT defects in human and mouse.
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- 2015
25. Cardio-Facio-Cutaneous Syndrome: Clinical Features, Diagnosis, and Management Guidelines
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Pierpont, Mary Ella M, Magoulas, Pilar L, Adi, Saleh, Kavamura, Maria Ines, Neri, Giovanni, Noonan, Jacqueline, Pierpont, Elizabeth I, Reinker, Kent, Roberts, Amy E, Shankar, Suma, Sullivan, Joseph, Wolford, Melinda, Conger, Brenda, Santa Cruz, Molly, and Rauen, Katherine A
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Biomedical and Clinical Sciences ,Clinical Sciences ,Brain Disorders ,Pediatric ,Rare Diseases ,Intellectual and Developmental Disabilities (IDD) ,Clinical Research ,Congenital Structural Anomalies ,7.3 Management and decision making ,Management of diseases and conditions ,Congenital ,Diagnosis ,Differential ,Disease Management ,Ectodermal Dysplasia ,Facies ,Failure to Thrive ,Genetic Testing ,Heart Defects ,Congenital ,Humans ,Practice Guidelines as Topic ,cardio-facio-cutaneous syndrome ,BRAF mutation ,management guidelines ,MEK1 mutation ,MEK2 mutation ,RASopathy ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Pediatrics ,Biomedical and clinical sciences ,Health sciences ,Psychology - Abstract
Cardio-facio-cutaneous syndrome (CFC) is one of the RASopathies that bears many clinical features in common with the other syndromes in this group, most notably Noonan syndrome and Costello syndrome. CFC is genetically heterogeneous and caused by gene mutations in the Ras/mitogen-activated protein kinase pathway. The major features of CFC include characteristic craniofacial dysmorphology, congenital heart disease, dermatologic abnormalities, growth retardation, and intellectual disability. It is essential that this condition be differentiated from other RASopathies, as a correct diagnosis is important for appropriate medical management and determining recurrence risk. Children and adults with CFC require multidisciplinary care from specialists, and the need for comprehensive management has been apparent to families and health care professionals caring for affected individuals. To address this need, CFC International, a nonprofit family support organization that provides a forum for information, support, and facilitation of research in basic medical and social issues affecting individuals with CFC, organized a consensus conference. Experts in multiple medical specialties provided clinical management guidelines for pediatricians and other care providers. These guidelines will assist in an accurate diagnosis of individuals with CFC, provide best practice recommendations, and facilitate long-term medical care.
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- 2014
26. Phenotypic Manifestations of Arrhythmogenic Cardiomyopathy in Children and Adolescents
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DeWitt, Elizabeth S., Chandler, Stephanie F., Hylind, Robyn J., Beausejour Ladouceur, Virginie, Blume, Elizabeth D., VanderPluym, Christina, Powell, Andrew J., Fynn-Thompson, Francis, Roberts, Amy E., Sanders, Stephen P., Bezzerides, Vassilios, Lakdawala, Neal K., MacRae, Calum A., and Abrams, Dominic J.
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- 2019
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27. Next-generation sequencing identifies rare variants associated with Noonan syndrome
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Chen, Peng-Chieh, Yin, Jiani, Yu, Hui-Wen, Yuan, Tao, Fernandez, Minerva, Yung, Christina K, Trinh, Quang M, Peltekova, Vanya D, Reid, Jeffrey G, Tworog-Dube, Erica, Morgan, Margaret B, Muzny, Donna M, Stein, Lincoln, McPherson, John D, Roberts, Amy E, Gibbs, Richard A, Neel, Benjamin G, and Kucherlapati, Raju
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Biological Sciences ,Bioinformatics and Computational Biology ,Biomedical and Clinical Sciences ,Genetics ,Congenital Structural Anomalies ,Rare Diseases ,Pediatric ,Neurosciences ,Brain Disorders ,Clinical Research ,2.1 Biological and endogenous factors ,Detection ,screening and diagnosis ,Aetiology ,4.1 Discovery and preclinical testing of markers and technologies ,Alleles ,Genetic Association Studies ,High-Throughput Nucleotide Sequencing ,Humans ,MAP Kinase Kinase 1 ,MAP Kinase Signaling System ,Mutation ,Neurofibromin 1 ,Noonan Syndrome ,ras Proteins ,human genetics ,developmental diseases ,whole exome sequencing ,PTPN11 ,RAS - Abstract
Noonan syndrome (NS) is a relatively common genetic disorder, characterized by typical facies, short stature, developmental delay, and cardiac abnormalities. Known causative genes account for 70-80% of clinically diagnosed NS patients, but the genetic basis for the remaining 20-30% of cases is unknown. We performed next-generation sequencing on germ-line DNA from 27 NS patients lacking a mutation in the known NS genes. We identified gain-of-function alleles in Ras-like without CAAX 1 (RIT1) and mitogen-activated protein kinase kinase 1 (MAP2K1) and previously unseen loss-of-function variants in RAS p21 protein activator 2 (RASA2) that are likely to cause NS in these patients. Expression of the mutant RASA2, MAP2K1, or RIT1 alleles in heterologous cells increased RAS-ERK pathway activation, supporting a causative role in NS pathogenesis. Two patients had more than one disease-associated variant. Moreover, the diagnosis of an individual initially thought to have NS was revised to neurofibromatosis type 1 based on an NF1 nonsense mutation detected in this patient. Another patient harbored a missense mutation in NF1 that resulted in decreased protein stability and impaired ability to suppress RAS-ERK activation; however, this patient continues to exhibit a NS-like phenotype. In addition, a nonsense mutation in RPS6KA3 was found in one patient initially diagnosed with NS whose diagnosis was later revised to Coffin-Lowry syndrome. Finally, we identified other potential candidates for new NS genes, as well as potential carrier alleles for unrelated syndromes. Taken together, our data suggest that next-generation sequencing can provide a useful adjunct to RASopathy diagnosis and emphasize that the standard clinical categories for RASopathies might not be adequate to describe all patients.
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- 2014
28. Association of genetic and sulcal traits with executive function in congenital heart disease.
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Maleyeff, Lara, Newburger, Jane W., Wypij, David, Thomas, Nina H., Anagnoustou, Evdokia, Brueckner, Martina, Chung, Wendy K., Cleveland, John, Cunningham, Sean, Gelb, Bruce D., Goldmuntz, Elizabeth, Hagler, Donald J, Huang, Hao, King, Eileen, McQuillen, Patrick, Miller, Thomas A., Norris‐Brilliant, Ami, Porter, George A., Roberts, Amy E., and Grant, P. Ellen
- Abstract
Objective: Persons with congenital heart disease (CHD) are at increased risk of neurodevelopmental disabilities, including impairments to executive function. Sulcal pattern features correlate with executive function in adolescents with single‐ventricle heart disease and tetralogy of Fallot. However, the interaction of sulcal pattern features with genetic and participant factors in predicting executive dysfunction is unknown. Methods: We studied sulcal pattern features, participant factors, and genetic risk for executive function impairment in a cohort with multiple CHD types using stepwise linear regression and machine learning. Results: Genetic factors, including predicted damaging de novo or rare inherited variants in neurodevelopmental disabilities risk genes, apolipoprotein E genotype, and principal components of sulcal pattern features were associated with executive function measures after adjusting for age at testing, sex, mother's education, and biventricular versus single‐ventricle CHD in a linear regression model. Using regression trees and bootstrap validation, younger participant age and larger alterations in sulcal pattern features were consistently identified as important predictors of decreased cognitive flexibility with left hemisphere graph topology often selected as the most important predictor. Inclusion of both sulcal pattern and genetic factors improved model fit compared to either alone. Interpretation: We conclude that sulcal measures remain important predictors of cognitive flexibility, and the model predicting executive outcomes is improved by inclusion of potential genetic sources of neurodevelopmental risk. If confirmed, measures of sulcal patterning may serve as early imaging biomarkers to identify those at heightened risk for future neurodevelopmental disabilities. [ABSTRACT FROM AUTHOR]
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- 2024
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29. Epilepsy in cardiofaciocutaneous syndrome: Clinical burden and response to anti‐seizure medication.
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Kenney‐Jung, Daniel L., Collazo‐Lopez, Josue E., Rogers, Dante J., Shanley, Ryan, Zatkalik, Abigail L., Whitmarsh, Ashley E., Roberts, Amy E., Zenker, Martin, and Pierpont, Elizabeth I.
- Abstract
Treatment‐resistant epilepsy is among the most serious complications of cardiofaciocutaneous syndrome (CFCS), a rare disorder caused by germline variants in the RAS‐MAPK signaling pathway. This study analyzed the clinical characteristics of epilepsy and response to anti‐seizure medications (ASMs) in a multinational CFCS cohort. A caregiver survey provided data regarding seizure history, use of ASMs and other treatment approaches, adverse effects, caregiver perception of treatment response, and neurological disease burden impact among individuals with CFCS. Results from 138 survey responses were quantitatively analyzed in conjunction with molecular genetic results and neurological records. The disease burden impact of CFCS was higher among individuals with epilepsy (n = 74/138), especially those with more severe seizure presentation. Oxcarbazepine, a sodium‐channel blocker, had the best seizure control profile with relatively infrequent adverse effects. The most commonly prescribed ASM, levetiracetam, demonstrated comparatively poor seizure control. ASM efficacy was generally similar for individuals with BRAF and MAP2K1 gene variants. The high proportion of patients with CFCS who experienced poor seizure control despite use of multiple ASMs highlights a substantial unmet treatment need. Prospective study of ASM efficacy and clinical trials of therapies to attenuate RAS‐MAPK signaling may improve avenues for clinical management. [ABSTRACT FROM AUTHOR]
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- 2024
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30. Natural History of Hypertrophic Cardiomyopathy in Noonan Syndrome With Multiple Lentigines
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Monda, Emanuele, primary, Prosnitz, Aaron, additional, Aiello, Rossella, additional, Lioncino, Michele, additional, Norrish, Gabrielle, additional, Caiazza, Martina, additional, Drago, Fabrizio, additional, Beattie, Meaghan, additional, Tartaglia, Marco, additional, Russo, Maria Giovanna, additional, Colan, Steven D., additional, Calcagni, Giulio, additional, Gelb, Bruce D., additional, Kaski, Juan Pablo, additional, Roberts, Amy E., additional, and Limongelli, Giuseppe, additional
- Published
- 2023
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31. Perspectives of Rare Disease Experts on Newborn Genome Sequencing
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Gold, Nina B., primary, Adelson, Sophia M., additional, Shah, Nidhi, additional, Williams, Shardae, additional, Bick, Sarah L., additional, Zoltick, Emilie S., additional, Gold, Jessica I., additional, Strong, Alanna, additional, Ganetzky, Rebecca, additional, Roberts, Amy E., additional, Walker, Melissa, additional, Holtz, Alexander M., additional, Sankaran, Vijay G., additional, Delmonte, Ottavia, additional, Tan, Weizhen, additional, Holm, Ingrid A., additional, Thiagarajah, Jay R., additional, Kamihara, Junne, additional, Comander, Jason, additional, Place, Emily, additional, Wiggs, Janey, additional, and Green, Robert C., additional
- Published
- 2023
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32. Evidence-Based Assessment of Congenital Heart Disease Genes to Enable Returning Results in a Genomic Study
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Griffin, Emily L., primary, Nees, Shannon N., additional, Morton, Sarah U., additional, Wynn, Julia, additional, Patel, Nihir, additional, Jobanputra, Vaidehi, additional, Robinson, Scott, additional, Kochav, Stephanie M., additional, Tao, Alice, additional, Andrews, Carli, additional, Cross, Nancy, additional, Geva, Judith, additional, Lanzilotta, Kristen, additional, Ritter, Alyssa, additional, Taillie, Eileen, additional, Thompson, Alexandra, additional, Meyer, Chris, additional, Akers, Rachel, additional, King, Eileen C., additional, Cnota, James F, additional, Kim, Richard W., additional, Porter, George A., additional, Brueckner, Martina, additional, Seidman, Christine E., additional, Shen, Yufeng, additional, Gelb, Bruce D., additional, Goldmuntz, Elizabeth, additional, Newburger, Jane W., additional, Roberts, Amy E., additional, and Chung, Wendy K., additional
- Published
- 2023
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- View/download PDF
33. 6 - Dysmorphology and syndromes
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Lacro, Ronald V. and Roberts, Amy E.
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- 2025
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34. 5 - Genetics of congenital heart disease
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Roberts, Amy E. and Lacro, Ronald V.
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- 2025
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35. Description of a case of distal 2p trisomy by array‐based comparative genomic hybridization: A high resolution genome‐wide investigation for chromosomal aneuploidy in a single assay
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Roberts, Amy E, Listewnik, Marc, Irons, Mira B, Mulliken, John B, Morton, Cynthia C, Kimonis, Virginia E, and Lee, Charles
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Abnormalities ,Multiple ,Aneuploidy ,Chromosomes ,Human ,Pair 2 ,Chromosomes ,Human ,Pair 9 ,Face ,Growth Disorders ,Heart Defects ,Congenital ,Humans ,In Situ Hybridization ,Fluorescence ,Infant ,Karyotyping ,Male ,Nucleic Acid Hybridization ,Translocation ,Genetic ,Trisomy ,Genetics ,Clinical Sciences - Published
- 2004
36. Clinical presentation of 13 patients with subtelomeric rearrangements and a review of the literature
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Roberts, Amy E, Cox, Gerald F, Kimonis, Virginia, Lamb, Allen, and Irons, Mira
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Biological Sciences ,Biomedical and Clinical Sciences ,Genetics ,Clinical Research ,Brain Disorders ,Pediatric ,Genetic Testing ,Abnormalities ,Multiple ,Child ,Child ,Preschool ,Chromosome Aberrations ,Chromosome Deletion ,Female ,Humans ,In Situ Hybridization ,Fluorescence ,Male ,Telomere ,Trisomy ,Clinical Sciences ,Clinical sciences - Abstract
To re-examine the potential clinical indications for subtelomeric FISH testing and to provide additional cases to the growing literature on subtelomeric abnormalities and their genotype-phenotype correlations, we present a single center case series of 13 patients with chromosomal abnormalities detected by subtelomeric FISH testing over a 21 month period. The most common abnormality involved chromosome 1p (23%). Partial monosomy was present in 69% of the patients, complex rearrangements in 23%, and partial trisomy in 8%. The mean time from first normal karyotype to positive subtelomeric FISH result was 3.8 years (n = 11, median 3.5 years, range: 6 months-10 years). One patient had an abnormal high resolution karyotype recognized retrospectively, and two other patients had abnormal karyotypes that were fully deciphered only after subtelomeric FISH analysis. Eighty five percent of cases occurred de novo. The subtelomeric FISH results were useful for adjusting the recurrence risks and helping to focus medical screening and monitoring. The results impacted family planning and satisfied families in search of a diagnosis. Our findings support the use of subtelomeric FISH analysis as a second tier test in patients suspected of having a chromosomal abnormality with a normal karyotype. Potential benefits of subtelomeric FISH testing include faster time to diagnosis, better informed patient prognosis, and more accurate genetic counseling.
- Published
- 2004
37. The Genetics of Neurodevelopment in Congenital Heart Disease
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Patt, Eli, primary, Singhania, Asmita, additional, Roberts, Amy E., additional, and Morton, Sarah U., additional
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- 2023
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38. Association of Potentially Damaging De Novo Gene Variants With Neurologic Outcomes in Congenital Heart Disease
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Morton, Sarah U., primary, Norris-Brilliant, Ami, additional, Cunningham, Sean, additional, King, Eileen, additional, Goldmuntz, Elizabeth, additional, Brueckner, Martina, additional, Miller, Thomas A., additional, Thomas, Nina H., additional, Liu, Chunyan, additional, Adams, Heather R., additional, Bellinger, David C., additional, Cleveland, John, additional, Cnota, James F., additional, Dale, Anders M., additional, Frommelt, Michele, additional, Gelb, Bruce D., additional, Grant, P. Ellen, additional, Goldberg, Caren S., additional, Huang, Hao, additional, Kuperman, Joshua M., additional, Li, Jennifer S., additional, McQuillen, Patrick S., additional, Panigrahy, Ashok, additional, Porter, George A., additional, Roberts, Amy E., additional, Russell, Mark W., additional, Seidman, Christine E., additional, Tivarus, Madalina E., additional, Anagnoustou, Evdokia, additional, Hagler, Donald J., additional, Chung, Wendy K., additional, and Newburger, Jane W., additional
- Published
- 2023
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39. Titin truncating mutations: A rare cause of dilated cardiomyopathy in the young
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Fatkin, Diane, Lam, Lien, Herman, Daniel S., Benson, Craig C., Felkin, Leanne E., Barton, Paul J.R., Walsh, Roddy, Candan, Sukru, Ware, James S., Roberts, Angharad M., Chung, Wendy K., Smoot, Leslie, Bornaun, Helen, Keogh, Anne M., Macdonald, Peter S., Hayward, Christopher S., Seidman, J.G., Roberts, Amy E., Cook, Stuart A., and Seidman, Christine E.
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- 2016
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40. morton_2023_oi_221502_1674145740.31597.pdf
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Morton, Sarah U, Norris-Brilliant, Ami, Cunningham, Sean, King, Eileen, Goldmuntz, Elizabeth, Brueckner, Martina, Miller, Thomas A., Thomas, Nina H., Liu, Chunyan, Adams, Heather R., Bellinger, David C, Cleveland, John, Cnota, James F., Dale, Anders M., Frommelt, Michele, Gelb, Bruce D., Grant, P. Ellen, Goldberg, Caren S., Huang, Hao, Kuperman, Joshua, Li, Jennifer S., McQuillen, Patrick, Panigrahy, Ashok, A. Porter Jr, George, Roberts, Amy E., Russell, Mark W., Seidman, Christine E., E. Tivarus, Madalina, Anagnoustou, Evdokia, J. Hagler Jr., Donald, Chung, Wendy K., and W Newburger, Jane
- Subjects
Cardiology (incl. cardiovascular diseases) - Abstract
Importance: Neurodevelopmental disabilities are commonly associated with congenital heart disease (CHD) but medical and sociodemographic factors explain only one third of variance in outcome. Objective: To determine whether predicted damaging de novo variants (dDNV) in genes not previously linked to neurodevelopmental disability are associated with neurologic outcomes in CHD. A post-hoc aim sought to determine whether some dDNV or rare predicted loss-of-function (pLOF) variants in specific gene categories are associated with outcomes. Design: Prospective observational study from September 2017-June 2020. Setting: Multicenter Participants: Participants were drawn from the Pediatric Cardiac Genomics Consortium (n=197) or Single Ventricle Reconstruction trial (n=24). Inclusion criteria were CHD, ≥ age 8 years, and available exome sequencing data. Individuals with pathogenic variants in known CHD- or neurodevelopmental-related genes were excluded. Cases and controls were frequency-matched for CHD class, age group, and sex. All 221 participants were included in post-hoc analyses, and 219 in case/control analysis. Exposure: Participants were heterozygous for (cases) or lacked (controls) predicted dDNV in genes not previously associated with neurodevelopmental disability. Participants were separately stratified as heterozygous or not heterozygous for dDNV or pLOF variants in four gene categories: chromatin-modifying, constrained, high-brain-expressed, and neurodevelopmental risk. Main Outcomes and Measures: Neurodevelopmental and brain MRI metrics. Results: Participants were median 15.0 years, interquartile range [IQR] 10.0-21.2; 50% (110/219) were male. Case and control participants had similar outcomes. dDNV/pLOF variants in chromatin-modifying genes were associated with worse verbal comprehension (n=16 vs. 200 participants, mean±SD: 91.4±20.4 vs. 103.4±17.8, p=0.01), social responsiveness (n=15 vs. 183, 57.3±17.2 vs. 49.4±11.2, p=0.03), and working memory (n=5 vs. 87, 73.8±16.4 vs. 97.3±15.7, p=0.03), as well as higher likelihood of autism spectrum disorder (4/14 vs. 8/153, 28.6% vs. 5.2%, p = 0.01). dDNV/pLOF variants in constrained genes were associated with impaired memory (immediated story memory: n=95 vs. 122, 9.7±3.7 vs. 10.7±3.0, p=0.03; immediate picture memory: n= 93 vs 116, 7.8±3.1 vs. 9.0±2.9, p=0.01). Adults with dDNV/pLOF variants in high-brain-expressed genes had greater hyperactivity symptoms (n=42 vs 33, 55.5±15.4 vs. 46.6±12.3, p=0.01). Conclusions and Relevance: Neurodevelopmental outcomes are not associated with dDNV as a group, but may be worse in those with dDNV/pLOF variants in some gene sets, such as chromatin-modifying genes. Future studies should confirm the importance of specific variants to brain function and structure.
- Published
- 2023
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41. 1-s2.0-S0828282X22009072-main.pdf
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Patt, Eli, Singhania, Asmita, Roberts, Amy E., and U. Morton, Sarah
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Cardiology (incl. cardiovascular diseases) - Abstract
Congenital heart disease (CHD) is the most common birth anomaly, affecting almost 1% of infants. Neurodevelopmental delay is the most common extracardiac feature in people with CHD. Many factors may contribute to neurodevelopmental risk, including genetic factors, CHD physiology, and the prenatal/postnatal environment. Damaging vari- ants are most highly enriched among individuals with extracardiac anomalies or neurodevelopmental delay in addition to CHD, indicating that genetic factors have an impact beyond cardiac tissues in people with CHD. Potential sources of genetic risk include large deletions or duplications that affect multiple genes, such as 22q11 deletion syn- drome, single genes that alter both heart and brain development, such as CHD7, and common variants that affect neurodevelopmental resiliency, such as APOE. Increased use of genome-sequencing tech- nologies in studies of neurodevelopmental outcomes in people with CHD will improve our ability to detect relevant genes and variants. Ultimately, such knowledge can lead to improved and more timely intervention of learning support for affected children.
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- 2023
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42. Insights Into the Pathogenesis of Catecholaminergic Polymorphic Ventricular Tachycardia From Engineered Human Heart Tissue
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Park, Sung-Jin, Zhang, Donghui, Qi, Yan, Li, Yifei, Lee, Keel Yong, Bezzerides, Vassilios J., Yang, Pengcheng, Xia, Shutao, Kim, Sean L., Liu, Xujie, Lu, Fujian, Pasqualini, Francesco S., Campbell, Patrick H., Geva, Judith, Roberts, Amy E., Kleber, Andre G., Abrams, Dominic J., Pu, William T., and Parker, Kevin Kit
- Published
- 2019
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43. Inducible Pluripotent Stem Cell–Derived Cardiomyocytes Reveal Aberrant Extracellular Regulated Kinase 5 and Mitogen-Activated Protein Kinase Kinase 1/2 Signaling Concomitantly Promote Hypertrophic Cardiomyopathy in RAF1-Associated Noonan Syndrome
- Author
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Jaffré, Fabrice, Miller, Clint L., Schänzer, Anne, Evans, Todd, Roberts, Amy E., Hahn, Andreas, and Kontaridis, Maria I.
- Published
- 2019
- Full Text
- View/download PDF
44. How to effectively utilize genetic testing in the care of children with cardiomyopathies
- Author
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Russell, Mark, Roberts, Amy E., Abrams, Dominic J., Murphy, Anne M., Towbin, Jeffrey A., and Chung, Wendy K.
- Published
- 2015
- Full Text
- View/download PDF
45. Cardiomyopathies in Noonan syndrome and the other RASopathies
- Author
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Gelb, Bruce D., Roberts, Amy E., and Tartaglia, Marco
- Published
- 2015
- Full Text
- View/download PDF
46. The Integral Formation of Catholic School Teachers
- Author
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Roberts, Amy E., primary and O’Shea, Gerard, additional
- Published
- 2022
- Full Text
- View/download PDF
47. Infantile epileptic spasms syndrome in children with cardiofaciocutanous syndrome: Clinical presentation and associations with genotype
- Author
-
Kenney‐Jung, Daniel L., primary, Rogers, Dante J., additional, Kroening, Samuel J., additional, Zatkalik, Abigail L., additional, Whitmarsh, Ashley E., additional, Roberts, Amy E., additional, Zenker, Martin, additional, Gambardella, Maria Luigia, additional, Contaldo, Ilaria, additional, Leoni, Chiara, additional, Onesimo, Roberta, additional, Zampino, Giuseppe, additional, Tartaglia, Marco, additional, Battaglia, Domenica I., additional, and Pierpont, Elizabeth I., additional
- Published
- 2022
- Full Text
- View/download PDF
48. Development of the Cardiovascular System
- Author
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Kussman, Barry D., primary, Roberts, Amy E., additional, and Miller‐Hance, Wanda C., additional
- Published
- 2022
- Full Text
- View/download PDF
49. Neurologic and neurodevelopmental complications in cardiofaciocutaneous syndrome are associated with genotype: A multinational cohort study
- Author
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Pierpont, Elizabeth I., primary, Kenney-Jung, Daniel L., additional, Shanley, Ryan, additional, Zatkalik, Abigail L., additional, Whitmarsh, Ashley E., additional, Kroening, Samuel J., additional, Roberts, Amy E., additional, and Zenker, Martin, additional
- Published
- 2022
- Full Text
- View/download PDF
50. Heart Failure in Congenital Heart Disease: A Confluence of Acquired and Congenital
- Author
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Fahed, Akl C., Roberts, Amy E., Mital, Seema, and Lakdawala, Neal K.
- Published
- 2014
- Full Text
- View/download PDF
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