943 results on '"Klee, Eric W"'
Search Results
2. Deep Phenotyping of Non-Alcoholic Fatty Liver Disease Patients with Genetic Factors for Insights into the Complex Disease
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Priya, Tahmina Sultana, Leng, Fan, Luehrs, Anthony C., Klee, Eric W., Allen, Alina M., Lazaridis, Konstantinos N., Danfeng, Yao, and Tian, Shulan
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Quantitative Biology - Quantitative Methods ,Computer Science - Machine Learning - Abstract
Non-alcoholic fatty liver disease (NAFLD) is a prevalent chronic liver disorder characterized by the excessive accumulation of fat in the liver in individuals who do not consume significant amounts of alcohol, including risk factors like obesity, insulin resistance, type 2 diabetes, etc. We aim to identify subgroups of NAFLD patients based on demographic, clinical, and genetic characteristics for precision medicine. The genomic and phenotypic data (3,408 cases and 4,739 controls) for this study were gathered from participants in Mayo Clinic Tapestry Study (IRB#19-000001) and their electric health records, including their demographic, clinical, and comorbidity data, and the genotype information through whole exome sequencing performed at Helix using the Exome+$^\circledR$ Assay according to standard procedure (www$.$helix$.$com). Factors highly relevant to NAFLD were determined by the chi-square test and stepwise backward-forward regression model. Latent class analysis (LCA) was performed on NAFLD cases using significant indicator variables to identify subgroups. The optimal clustering revealed 5 latent subgroups from 2,013 NAFLD patients (mean age 60.6 years and 62.1% women), while a polygenic risk score based on 6 single-nucleotide polymorphism (SNP) variants and disease outcomes were used to analyze the subgroups. The groups are characterized by metabolic syndrome, obesity, different comorbidities, psychoneurological factors, and genetic factors. Odds ratios were utilized to compare the risk of complex diseases, such as fibrosis, cirrhosis, and hepatocellular carcinoma (HCC), as well as liver failure between the clusters. Cluster 2 has a significantly higher complex disease outcome compared to other clusters. Keywords: Fatty liver disease; Polygenic risk score; Precision medicine; Deep phenotyping; NAFLD comorbidities; Latent class analysis., Comment: Extended Abstract presented at Machine Learning for Health (ML4H) symposium 2023, December 10th, 2023, New Orleans, United States, 11 pages
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- 2023
3. Diagnostic yield of exome and genome sequencing after non-diagnostic multi-gene panels in patients with single-system diseases
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Wilke, Matheus V. M. B., Klee, Eric W., Dhamija, Radhika, Fervenza, Fernando C., Thomas, Brittany, Leung, Nelson, Hogan, Marie C., Hager, Megan M., Kolbert, Kayla J., Kemppainen, Jennifer L., Loftus, Elle C., Leitzen, Katie M., Vitek, Carolyn R., McAllister, Tammy, Lazaridis, Konstantinos N., and Pinto e Vairo, Filippo
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- 2024
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4. Correction: Implementation of genomic medicine for rare disease in a tertiary healthcare system: Mayo Clinic Program for Rare and Undiagnosed Diseases (PRaUD)
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Pinto e Vairo, Filippo, Kemppainen, Jennifer L., Vitek, Carolyn R. Rohrer, Whalen, Denise A., Kolbert, Kayla J., Sikkink, Kaitlin J., Kroc, Sarah A., Kruisselbrink, Teresa, Shupe, Gabrielle F., Knudson, Alyssa K., Burke, Elizabeth M., Loftus, Elle C., Bandel, Lorelei A., Prochnow, Carri A., Mulvihill, Lindsay A., Thomas, Brittany, Gable, Dale M., Graddy, Courtney B., Garzon, Giovanna G. Moreno, Ekpoh, Idara U., Porquera, Eva M. Carmona, Fervenza, Fernando C., Hogan, Marie C., El Ters, Mireille, Warrington, Kenneth J., Davis, III, John M., Koster, Matthew J., Orandi, Amir B., Basiaga, Matthew L., Vella, Adrian, Kumar, Seema, Creo, Ana L., Lteif, Aida N., Pittock, Siobhan T., Tebben, Peter J., Abate, Ejigayehu G., Joshi, Avni Y., Ristagno, Elizabeth H., Patnaik, Mrinal S., Schimmenti, Lisa A., Dhamija, Radhika, Sabrowsky, Sonia M., Wierenga, Klaas J., Keddis, Mira T., Samadder, Niloy Jewel J., Presutti, Richard J., Robinson, Steven I., Stephens, Michael C., Roberts, Lewis R., Faubion, Jr., William A., Driscoll, Sherilyn W., Wong-Kisiel, Lily C., Selcen, Duygu, Flanagan, Eoin P., Ramanan, Vijay K., Jackson, Lauren M., Mauermann, Michelle L., Ortega, Victor E., Anderson, Sarah A., Aoudia, Stacy L., Klee, Eric W., McAllister, Tammy M., and Lazaridis, Konstantinos N.
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- 2024
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5. Identification of skewed X chromosome inactivation using exome and transcriptome sequencing in patients with suspected rare genetic disease
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Fadra, Numrah, Schultz-Rogers, Laura E, Chanana, Pritha, Cousin, Margot A, Macke, Erica L, Ferrer, Alejandro, Pinto e Vairo, Filippo, Olson, Rory J, Oliver, Gavin R, Mulvihill, Lindsay A, Jenkinson, Garrett, and Klee, Eric W
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- 2024
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6. Bi-allelic variants in CELSR3 are implicated in central nervous system and urinary tract anomalies
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Stegmann, Jil D., Kalanithy, Jeshurun C., Dworschak, Gabriel C., Ishorst, Nina, Mingardo, Enrico, Lopes, Filipa M., Ho, Yee Mang, Grote, Phillip, Lindenberg, Tobias T., Yilmaz, Öznur, Channab, Khadija, Seltzsam, Steve, Shril, Shirlee, Hildebrandt, Friedhelm, Boschann, Felix, Heinen, André, Jolly, Angad, Myers, Katherine, McBride, Kim, Bekheirnia, Mir Reza, Bekheirnia, Nasim, Scala, Marcello, Morleo, Manuela, Nigro, Vincenzo, Torella, Annalaura, Pinelli, Michele, Capra, Valeria, Accogli, Andrea, Maitz, Silvia, Spano, Alice, Olson, Rory J., Klee, Eric W., Lanpher, Brendan C., Jang, Se Song, Chae, Jong-Hee, Steinbauer, Philipp, Rieder, Dietmar, Janecke, Andreas R., Vodopiutz, Julia, Vogel, Ida, Blechingberg, Jenny, Cohen, Jennifer L., Riley, Kacie, Klee, Victoria, Walsh, Laurence E., Begemann, Matthias, Elbracht, Miriam, Eggermann, Thomas, Stoppe, Arzu, Stuurman, Kyra, van Slegtenhorst, Marjon, Barakat, Tahsin Stefan, Mulhern, Maureen S., Sands, Tristan T., Cytrynbaum, Cheryl, Weksberg, Rosanna, Isidori, Federica, Pippucci, Tommaso, Severi, Giulia, Montanari, Francesca, Kruer, Michael C., Bakhtiari, Somayeh, Darvish, Hossein, Reutter, Heiko, Hagelueken, Gregor, Geyer, Matthias, Woolf, Adrian S., Posey, Jennifer E., Lupski, James R., Odermatt, Benjamin, and Hilger, Alina C.
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- 2024
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7. Semiautomated approach focused on new genomic information results in time and effort-efficient reannotation of negative exome data
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Ferrer, Alejandro, Duffy, Patrick, Olson, Rory J., Meiners, Michael A., Schultz-Rogers, Laura, Macke, Erica L., Safgren, Stephanie, Morales-Rosado, Joel A., Cousin, Margot A., Oliver, Gavin R., Rider, David, Williams, Megan, Pichurin, Pavel N., Deyle, David R., Morava, Eva, Gavrilova, Ralitza H., Dhamija, Radhika, Wierenga, Klass J., Lanpher, Brendan C., Babovic-Vuksanovic, Dusica, Kaiwar, Charu, Vitek, Carolyn R., McAllister, Tammy M., Wick, Myra J., Schimmenti, Lisa A., Lazaridis, Konstantinos N., Vairo, Filippo Pinto e, and Klee, Eric W.
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- 2024
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8. MARK2 variants cause autism spectrum disorder via the downregulation of WNT/β-catenin signaling pathway
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Gong, Maolei, Li, Jiayi, Qin, Zailong, Machado Bressan Wilke, Matheus Vernet, Liu, Yijun, Li, Qian, Liu, Haoran, Liang, Chen, Morales-Rosado, Joel A., Cohen, Ana S.A., Hughes, Susan S., Sullivan, Bonnie R., Waddell, Valerie, van den Boogaard, Marie-José H., van Jaarsveld, Richard H., van Binsbergen, Ellen, van Gassen, Koen L., Wang, Tianyun, Hiatt, Susan M., Amaral, Michelle D., Kelley, Whitley V., Zhao, Jianbo, Feng, Weixing, Ren, Changhong, Yu, Yazhen, Boczek, Nicole J., Ferber, Matthew J., Lahner, Carrie, Elliott, Sherr, Ruan, Yiyan, Mignot, Cyril, Keren, Boris, Xie, Hua, Wang, Xiaoyan, Popp, Bernt, Zweier, Christiane, Piard, Juliette, Coubes, Christine, Mau-Them, Frederic Tran, Safraou, Hana, Innes, A. Micheil, Gauthier, Julie, Michaud, Jacques L., Koboldt, Daniel C., Sylvie, Odent, Willems, Marjolaine, Tan, Wen-Hann, Cogne, Benjamin, Rieubland, Claudine, Braun, Dominique, McLean, Scott Douglas, Platzer, Konrad, Zacher, Pia, Oppermann, Henry, Evenepoel, Lucie, Blanc, Pierre, El Khattabi, Laïla, Haque, Neshatul, Dsouza, Nikita R., Zimmermann, Michael T., Urrutia, Raul, Klee, Eric W., Shen, Yiping, Du, Hongzhen, Rappaport, Leonard, Liu, Chang-Mei, and Chen, Xiaoli
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- 2024
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9. Prevalence, Penetrance, and Phenotypic Manifestation of Cardiomyopathy-Associated Genetic Variants in the General Population: Insights from a Mayo Clinic Biobank Study
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Figueiral, Marta, Paldino, Alessia, Wilke, Matheus Vernet Machado Bressan, Farris, Joseph D., Verheijen, Jan, Giudicessi, John R., Ackerman, Michael J., Olson, Janet E., Arroyo, Jennifer, Olson, Rory J., Klee, Eric W., and Pereira, Naveen L.
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- 2024
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10. Exome Sequencing Identifies Carriers of the Autosomal Dominant Cancer Predisposition Disorders Beyond Current Practice Guideline Recommendations
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Samadder, N. Jewel, Gay, Emily, Lindpere, Vanda, Bublitz, Michelle L., Bandel, Lorelei A., Armasu, Sebastian M., Vierkant, Robert A., Ferber, Matthew J., Klee, Eric W., Larson, Nicholas B., Kruisselbrink, Teresa M., Egan, Jan B., Kemppainen, Jennifer L., Bidwell, Jessa S., Anderson, Jennifer L., McAllister, Tammy M., Walker, TʼNita S., Kunze, Katie L., Golafshar, Michael A., Klint, Margaret A., Presutti, Richard J., Bobo, William V., Sekulic, Aleksander, Summer-Bolster, Jolene M., Willman, Cheryl L., and Lazaridis, Konstantinos N.
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- 2024
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11. Universally Rank Consistent Ordinal Regression in Neural Networks
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Jenkinson, Garrett, Oliver, Gavin R., Khezeli, Kia, Kalantari, John, and Klee, Eric W.
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Computer Science - Machine Learning - Abstract
Despite the pervasiveness of ordinal labels in supervised learning, it remains common practice in deep learning to treat such problems as categorical classification using the categorical cross entropy loss. Recent methods attempting to address this issue while respecting the ordinal structure of the labels have resorted to converting ordinal regression into a series of extended binary classification subtasks. However, the adoption of such methods remains inconsistent due to theoretical and practical limitations. Here we address these limitations by demonstrating that the subtask probabilities form a Markov chain. We show how to straightforwardly modify neural network architectures to exploit this fact and thereby constrain predictions to be universally rank consistent. We furthermore prove that all rank consistent solutions can be represented within this formulation, and derive a loss function producing maximum likelihood parameter estimates. Using diverse benchmarks and the real-world application of a specialized recurrent neural network for COVID-19 prognosis, we demonstrate the practical superiority of this method versus the current state-of-the-art. The method is open sourced as user-friendly PyTorch and TensorFlow packages.
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- 2021
12. Menke-Hennekam syndrome; delineation of domain-specific subtypes with distinct clinical and DNA methylation profiles
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Angius, Andrea, Baker, Janice A., Bedoukian, Emma, Bhambhani, Vikas, Bodamer, Olaf, O’Brien, Alan, Clayton-Smith, Jill, Crisponi, Laura, Cueto González, Anna María, the DDD study, Devriendt, Koenraad, Garrido, Elena Dominguez, Ehmke, Nadja, van Eerde, Albertien, van den Elzen, Annette P.M., Faivre, Laurence, Fisher, Laura, Flores-Daboub, Josue A., Foster, Alison, Friedman, Jennifer, Gabau, Elisabeth, Galazzi, Elena, García-Miñaúr, Sixto, Garavelli, Livia, Gardeitchik, Thatjana, Gerkes, Erica H., van Gils, Julien, Giltay, Jacques C., Garcia, Aixa Gonzalez, Heimdal, Ketil Riddervold, Horn, Denise, Houge, Gunnar, Hufnagel, Sophia B., Ilencikova, Denisa, Julia, Sophie, Kant, Sarina G., Kinning, Esther, Klee, Eric W., Kois, Chelsea, Kovačević, Maja, Lachmeijer, A.M.A. (Guus), Lanpher, Brendan, Lebrun, Marine, Leon, Eyby, Lichty, Angie Ward, Lin, Ruth, Llano-Rivas, Isabel, Lynch, Sally Ann, Maas, Saskia M., Maitz, Silvia B., McKee, Shane, Melis, Daniela, Merati, Elisabetta, Merla, Giuseppe, Newbury-Ecob, Ruth, Nizon, Mathilde, Park, Soo-Mi, Patterson, Jennifer, Petit, Florence, Peeters, Hilde, Persani, Luca, Persico, Ivana, Pes, Valentina, Pollazzon, Marzia, Potjer, Thomas, Potocki, Lorraine, Pottinger, Carrie, Prasad, Chitra, Prijoles, Eloise J., Ragge, Nicola K., Rake, Jan Peter, van Ravenswaaij-Arts, Conny M.A., Rea, Gillian, Ruivenkamp, Claudia, Rutz, Audrey, Saitta, Sulagna C., Russo, Rossana Sanchez, Santen, Gijs W.E., Schaefer, Elise, Shashi, Vandana, Schultz-Rogers, Laura, Sluga, Andrea, Sotgiu, Stefano, Steichen-Gersdorf, Elisabeth, Sullivan, Jennifer A., Sun, Yu, Suri, Mohnish, Tartaglia, Marco, Tedder, Matt, Terhal, Paulien, Tully, Ian, Verbeek, Nienke, Wenzel, Maren, White, Susan M., Xiao, Bing, Haghshenas, Sadegheh, Bout, Hidde J., Schijns, Josephine M., Levy, Michael A., Kerkhof, Jennifer, Bhai, Pratibha, McConkey, Haley, Jenkins, Zandra A., Williams, Ella M., Halliday, Benjamin J., Huisman, Sylvia A., Lauffer, Peter, de Waard, Vivian, Witteveen, Laura, Banka, Siddharth, Brady, Angela F., Hurst, Anna C.E., Kaiser, Frank J., Lacombe, Didier, Martinez-Monseny, Antonio F., Fergelot, Patricia, Monteiro, Fabíola P., Parenti, Ilaria, Santos-Simarro, Fernando, Simpson, Brittany N., Alders, Mariëlle, Robertson, Stephen P., Sadikovic, Bekim, and Menke, Leonie A.
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- 2024
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13. Implementation of genomic medicine for rare disease in a tertiary healthcare system: Mayo Clinic Program for Rare and Undiagnosed Diseases (PRaUD)
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Pinto e Vairo, Filippo, Kemppainen, Jennifer L., Vitek, Carolyn R. Rohrer, Whalen, Denise A., Kolbert, Kayla J., Sikkink, Kaitlin J., Kroc, Sarah A., Kruisselbrink, Teresa, Shupe, Gabrielle F., Knudson, Alyssa K., Burke, Elizabeth M., Loftus, Elle C., Bandel, Lorelei A., Prochnow, Carri A., Mulvihill, Lindsay A., Thomas, Brittany, Gable, Dale M., Graddy, Courtney B., Garzon, Giovanna G. Moreno, Ekpoh, Idara U., Porquera, Eva M. Carmona, Fervenza, Fernando C., Hogan, Marie C., El Ters, Mireille, Warrington, Kenneth J., Davis, III, John M., Koster, Matthew J., Orandi, Amir B., Basiaga, Matthew L., Vella, Adrian, Kumar, Seema, Creo, Ana L., Lteif, Aida N., Pittock, Siobhan T., Tebben, Peter J., Abate, Ejigayehu G., Joshi, Avni Y., Ristagno, Elizabeth H., Patnaik, Mrinal S., Schimmenti, Lisa A., Dhamija, Radhika, Sabrowsky, Sonia M., Wierenga, Klaas J., Keddis, Mira T., Samadder, Niloy Jewel J., Presutti, Richard J., Robinson, Steven I., Stephens, Michael C., Roberts, Lewis R., Faubion, Jr., William A., Driscoll, Sherilyn W., Wong-Kisiel, Lily C., Selcen, Duygu, Flanagan, Eoin P., Ramanan, Vijay K., Jackson, Lauren M., Mauermann, Michelle L., Ortega, Victor E., Anderson, Sarah A., Aoudia, Stacy L., Klee, Eric W., McAllister, Tammy M., and Lazaridis, Konstantinos N.
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- 2023
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14. Truncating SRCAP variants outside the Floating-Harbor syndrome locus cause a distinct neurodevelopmental disorder with a specific DNA methylation signature
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Rots, Dmitrijs, Chater-Diehl, Eric, Dingemans, Alexander JM, Goodman, Sarah J, Siu, Michelle T, Cytrynbaum, Cheryl, Choufani, Sanaa, Hoang, Ny, Walker, Susan, Awamleh, Zain, Charkow, Joshua, Meyn, Stephen, Pfundt, Rolph, Rinne, Tuula, Gardeitchik, Thatjana, de Vries, Bert BA, Deden, A Chantal, Leenders, Erika, Kwint, Michael, Stumpel, Constance TRM, Stevens, Servi JC, Vermeulen, Jeroen R, van Harssel, Jeske VT, Bosch, Danielle GM, van Gassen, Koen LI, van Binsbergen, Ellen, de Geus, Christa M, Brackel, Hein, Hempel, Maja, Lessel, Davor, Denecke, Jonas, Slavotinek, Anne, Strober, Jonathan, Crunk, Amy, Folk, Leandra, Wentzensen, Ingrid M, Yang, Hui, Zou, Fanggeng, Millan, Francisca, Person, Richard, Xie, Yili, Liu, Shuxi, Ousager, Lilian B, Larsen, Martin, Schultz-Rogers, Laura, Morava, Eva, Klee, Eric W, Berry, Ian R, Campbell, Jennifer, Lindstrom, Kristin, Pruniski, Brianna, Neumeyer, Ann M, Radley, Jessica A, Phornphutkul, Chanika, Schmidt, Berkley, Wilson, William G, Õunap, Katrin, Reinson, Karit, Pajusalu, Sander, van Haeringen, Arie, Ruivenkamp, Claudia, Cuperus, Roos, Santos-Simarro, Fernando, Palomares-Bralo, María, Pacio-Míguez, Marta, Ritter, Alyssa, Bhoj, Elizabeth, Tønne, Elin, Tveten, Kristian, Cappuccio, Gerarda, Brunetti-Pierri, Nicola, Rowe, Leah, Bunn, Jason, Saenz, Margarita, Platzer, Konrad, Mertens, Mareike, Caluseriu, Oana, Nowaczyk, Małgorzata JM, Cohn, Ronald D, Kannu, Peter, Alkhunaizi, Ebba, Chitayat, David, Scherer, Stephen W, Brunner, Han G, Vissers, Lisenka ELM, Kleefstra, Tjitske, Koolen, David A, and Weksberg, Rosanna
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Genetics ,Clinical Research ,Brain Disorders ,Mental Health ,Intellectual and Developmental Disabilities (IDD) ,Aetiology ,2.1 Biological and endogenous factors ,Abnormalities ,Multiple ,Adenosine Triphosphatases ,Case-Control Studies ,Cohort Studies ,Craniofacial Abnormalities ,DNA Methylation ,Epigenesis ,Genetic ,Female ,Genetic Predisposition to Disease ,Growth Disorders ,Heart Septal Defects ,Ventricular ,Humans ,Infant ,Newborn ,Male ,Mutation ,Neurodevelopmental Disorders ,Phenotype ,DNA methylation signature ,Floating-Harbor syndrome ,SRCAP ,epigenomics ,genotype-phenotype correlation ,intellectual disability ,neurodevelopmental disorders ,non-FLHS SRCAP-related NDD ,nonsense-mediated decay ,speech delay ,Biological Sciences ,Medical and Health Sciences ,Genetics & Heredity - Abstract
Truncating variants in exons 33 and 34 of the SNF2-related CREBBP activator protein (SRCAP) gene cause the neurodevelopmental disorder (NDD) Floating-Harbor syndrome (FLHS), characterized by short stature, speech delay, and facial dysmorphism. Here, we present a cohort of 33 individuals with clinical features distinct from FLHS and truncating (mostly de novo) SRCAP variants either proximal (n = 28) or distal (n = 5) to the FLHS locus. Detailed clinical characterization of the proximal SRCAP individuals identified shared characteristics: developmental delay with or without intellectual disability, behavioral and psychiatric problems, non-specific facial features, musculoskeletal issues, and hypotonia. Because FLHS is known to be associated with a unique set of DNA methylation (DNAm) changes in blood, a DNAm signature, we investigated whether there was a distinct signature associated with our affected individuals. A machine-learning model, based on the FLHS DNAm signature, negatively classified all our tested subjects. Comparing proximal variants with typically developing controls, we identified a DNAm signature distinct from the FLHS signature. Based on the DNAm and clinical data, we refer to the condition as "non-FLHS SRCAP-related NDD." All five distal variants classified negatively using the FLHS DNAm model while two classified positively using the proximal model. This suggests divergent pathogenicity of these variants, though clinically the distal group presented with NDD, similar to the proximal SRCAP group. In summary, for SRCAP, there is a clear relationship between variant location, DNAm profile, and clinical phenotype. These results highlight the power of combined epigenetic, molecular, and clinical studies to identify and characterize genotype-epigenotype-phenotype correlations.
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- 2021
15. Dominant-negative heterozygous mutations in AIRE confer diverse autoimmune phenotypes
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Oftedal, Bergithe E., Assing, Kristian, Baris, Safa, Safgren, Stephanie L., Johansen, Isik S., Jakobsen, Marianne Antonius, Babovic-Vuksanovic, Dusica, Agre, Katherine, Klee, Eric W., Majcic, Emina, Ferré, Elise M.N., Schmitt, Monica M., DiMaggio, Tom, Rosen, Lindsey B., Rahman, Muhammad Obaidur, Chrysis, Dionisios, Giannakopoulos, Aristeidis, Garcia, Maria Tallon, González-Granado, Luis Ignacio, Stanley, Katherine, Galant-Swafford, Jessica, Suwannarat, Pim, Meyts, Isabelle, Lionakis, Michail S., and Husebye, Eystein S.
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- 2023
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16. Widening of the genetic and clinical spectrum of Lamb–Shaffer syndrome, a neurodevelopmental disorder due to SOX5 haploinsufficiency
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Zawerton, Ash, Mignot, Cyril, Sigafoos, Ashley, Blackburn, Patrick R, Haseeb, Abdul, McWalter, Kirsty, Ichikawa, Shoji, Nava, Caroline, Keren, Boris, Charles, Perrine, Marey, Isabelle, Tabet, Anne-Claude, Levy, Jonathan, Perrin, Laurence, Hartmann, Andreas, Lesca, Gaetan, Schluth-Bolard, Caroline, Monin, Pauline, Dupuis-Girod, Sophie, Guillen Sacoto, Maria J, Schnur, Rhonda E, Zhu, Zehua, Poisson, Alice, El Chehadeh, Salima, Alembik, Yves, Bruel, Ange-Line, Lehalle, Daphné, Nambot, Sophie, Moutton, Sébastien, Odent, Sylvie, Jaillard, Sylvie, Dubourg, Christèle, Hilhorst-Hofstee, Yvonne, Barbaro-Dieber, Tina, Ortega, Lucia, Bhoj, Elizabeth J, Masser-Frye, Diane, Bird, Lynne M, Lindstrom, Kristin, Ramsey, Keri M, Narayanan, Vinodh, Fassi, Emily, Willing, Marcia, Cole, Trevor, Salter, Claire G, Akilapa, Rhoda, Vandersteen, Anthony, Canham, Natalie, Rump, Patrick, Gerkes, Erica H, Klein Wassink-Ruiter, Jolien S, Bijlsma, Emilia, Hoffer, Mariëtte JV, Vargas, Marcelo, Wojcik, Antonina, Cherik, Florian, Francannet, Christine, Rosenfeld, Jill A, Machol, Keren, Scott, Daryl A, Bacino, Carlos A, Wang, Xia, Clark, Gary D, Bertoli, Marta, Zwolinski, Simon, Thomas, Rhys H, Akay, Ela, Chang, Richard C, Bressi, Rebekah, Sanchez Russo, Rossana, Srour, Myriam, Russell, Laura, Goyette, Anne-Marie E, Dupuis, Lucie, Mendoza-Londono, Roberto, Karimov, Catherine, Joseph, Maries, Nizon, Mathilde, Cogné, Benjamin, Kuechler, Alma, Piton, Amélie, Klee, Eric W, Lefebvre, Véronique, Clark, Karl J, and Depienne, Christel
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Intellectual and Developmental Disabilities (IDD) ,Pediatric ,Genetics ,Brain Disorders ,Clinical Research ,Rare Diseases ,Human Genome ,Aetiology ,2.1 Biological and endogenous factors ,Adolescent ,Adult ,Animals ,Child ,Child ,Preschool ,DNA-Binding Proteins ,Female ,Genetic Predisposition to Disease ,Haploinsufficiency ,Humans ,Infant ,Intellectual Disability ,Language Development Disorders ,Male ,Mutation ,Missense ,Neurodevelopmental Disorders ,Pedigree ,Phenotype ,SOXD Transcription Factors ,Young Adult ,autism ,developmental delay ,intellectual disability ,epilepsy ,missense variants ,Deciphering Developmental DisorderStudy ,missense variants. ,Clinical Sciences ,Genetics & Heredity - Abstract
PurposeLamb-Shaffer syndrome (LAMSHF) is a neurodevelopmental disorder described in just over two dozen patients with heterozygous genetic alterations involving SOX5, a gene encoding a transcription factor regulating cell fate and differentiation in neurogenesis and other discrete developmental processes. The genetic alterations described so far are mainly microdeletions. The present study was aimed at increasing our understanding of LAMSHF, its clinical and genetic spectrum, and the pathophysiological mechanisms involved.MethodsClinical and genetic data were collected through GeneMatcher and clinical or genetic networks for 41 novel patients harboring various types ofSOX5 alterations. Functional consequences of selected substitutions were investigated.ResultsMicrodeletions and truncating variants occurred throughout SOX5. In contrast, most missense variants clustered in the pivotal SOX-specific high-mobility-group domain. The latter variants prevented SOX5 from binding DNA and promoting transactivation in vitro, whereas missense variants located outside the high-mobility-group domain did not. Clinical manifestations and severity varied among patients. No clear genotype-phenotype correlations were found, except that missense variants outside the high-mobility-group domain were generally better tolerated.ConclusionsThis study extends the clinical and genetic spectrum associated with LAMSHF and consolidates evidence that SOX5 haploinsufficiency leads to variable degrees of intellectual disability, language delay, and other clinical features.
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- 2020
17. Loss-of-function mutations in UDP-Glucose 6-Dehydrogenase cause recessive developmental epileptic encephalopathy.
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Hengel, Holger, Bosso-Lefèvre, Célia, Grady, George, Szenker-Ravi, Emmanuelle, Li, Hankun, Pierce, Sarah, Lebigot, Élise, Tan, Thong-Teck, Eio, Michelle Y, Narayanan, Gunaseelan, Utami, Kagistia Hana, Yau, Monica, Handal, Nader, Deigendesch, Werner, Keimer, Reinhard, Marzouqa, Hiyam M, Gunay-Aygun, Meral, Muriello, Michael J, Verhelst, Helene, Weckhuysen, Sarah, Mahida, Sonal, Naidu, Sakkubai, Thomas, Terrence G, Lim, Jiin Ying, Tan, Ee Shien, Haye, Damien, Willemsen, Michèl AAP, Oegema, Renske, Mitchell, Wendy G, Pierson, Tyler Mark, Andrews, Marisa V, Willing, Marcia C, Rodan, Lance H, Barakat, Tahsin Stefan, van Slegtenhorst, Marjon, Gavrilova, Ralitza H, Martinelli, Diego, Gilboa, Tal, Tamim, Abdullah M, Hashem, Mais O, AlSayed, Moeenaldeen D, Abdulrahim, Maha M, Al-Owain, Mohammed, Awaji, Ali, Mahmoud, Adel AH, Faqeih, Eissa A, Asmari, Ali Al, Algain, Sulwan M, Jad, Lamyaa A, Aldhalaan, Hesham M, Helbig, Ingo, Koolen, David A, Riess, Angelika, Kraegeloh-Mann, Ingeborg, Bauer, Peter, Gulsuner, Suleyman, Stamberger, Hannah, Ng, Alvin Yu Jin, Tang, Sha, Tohari, Sumanty, Keren, Boris, Schultz-Rogers, Laura E, Klee, Eric W, Barresi, Sabina, Tartaglia, Marco, Mor-Shaked, Hagar, Maddirevula, Sateesh, Begtrup, Amber, Telegrafi, Aida, Pfundt, Rolph, Schüle, Rebecca, Ciruna, Brian, Bonnard, Carine, Pouladi, Mahmoud A, Stewart, James C, Claridge-Chang, Adam, Lefeber, Dirk J, Alkuraya, Fowzan S, Mathuru, Ajay S, Venkatesh, Byrappa, Barycki, Joseph J, Simpson, Melanie A, Jamuar, Saumya S, Schöls, Ludger, and Reversade, Bruno
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Organoids ,Animals ,Zebrafish ,Humans ,Epilepsy ,Syndrome ,Oxidoreductases ,Pedigree ,Kinetics ,Genes ,Recessive ,Alleles ,Adolescent ,Child ,Child ,Preschool ,Infant ,Female ,Male ,Protein Domains ,Loss of Function Mutation ,Preschool ,Genes ,Recessive - Abstract
Developmental epileptic encephalopathies are devastating disorders characterized by intractable epileptic seizures and developmental delay. Here, we report an allelic series of germline recessive mutations in UGDH in 36 cases from 25 families presenting with epileptic encephalopathy with developmental delay and hypotonia. UGDH encodes an oxidoreductase that converts UDP-glucose to UDP-glucuronic acid, a key component of specific proteoglycans and glycolipids. Consistent with being loss-of-function alleles, we show using patients' primary fibroblasts and biochemical assays, that these mutations either impair UGDH stability, oligomerization, or enzymatic activity. In vitro, patient-derived cerebral organoids are smaller with a reduced number of proliferating neuronal progenitors while mutant ugdh zebrafish do not phenocopy the human disease. Our study defines UGDH as a key player for the production of extracellular matrix components that are essential for human brain development. Based on the incidence of variants observed, UGDH mutations are likely to be a frequent cause of recessive epileptic encephalopathy.
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- 2020
18. Partial Loss of USP9X Function Leads to a Male Neurodevelopmental and Behavioral Disorder Converging on Transforming Growth Factor β Signaling.
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Johnson, Brett V, Kumar, Raman, Oishi, Sabrina, Alexander, Suzy, Kasherman, Maria, Vega, Michelle Sanchez, Ivancevic, Atma, Gardner, Alison, Domingo, Deepti, Corbett, Mark, Parnell, Euan, Yoon, Sehyoun, Oh, Tracey, Lines, Matthew, Lefroy, Henrietta, Kini, Usha, Van Allen, Margot, Grønborg, Sabine, Mercier, Sandra, Küry, Sébastien, Bézieau, Stéphane, Pasquier, Laurent, Raynaud, Martine, Afenjar, Alexandra, Billette de Villemeur, Thierry, Keren, Boris, Désir, Julie, Van Maldergem, Lionel, Marangoni, Martina, Dikow, Nicola, Koolen, David A, VanHasselt, Peter M, Weiss, Marjan, Zwijnenburg, Petra, Sa, Joaquim, Reis, Claudia Falcao, López-Otín, Carlos, Santiago-Fernández, Olaya, Fernández-Jaén, Alberto, Rauch, Anita, Steindl, Katharina, Joset, Pascal, Goldstein, Amy, Madan-Khetarpal, Suneeta, Infante, Elena, Zackai, Elaine, Mcdougall, Carey, Narayanan, Vinodh, Ramsey, Keri, Mercimek-Andrews, Saadet, Pena, Loren, Shashi, Vandana, Undiagnosed Diseases Network, Schoch, Kelly, Sullivan, Jennifer A, Pinto E Vairo, Filippo, Pichurin, Pavel N, Ewing, Sarah A, Barnett, Sarah S, Klee, Eric W, Perry, M Scott, Koenig, Mary Kay, Keegan, Catherine E, Schuette, Jane L, Asher, Stephanie, Perilla-Young, Yezmin, Smith, Laurie D, Rosenfeld, Jill A, Bhoj, Elizabeth, Kaplan, Paige, Li, Dong, Oegema, Renske, van Binsbergen, Ellen, van der Zwaag, Bert, Smeland, Marie Falkenberg, Cutcutache, Ioana, Page, Matthew, Armstrong, Martin, Lin, Angela E, Steeves, Marcie A, Hollander, Nicolette den, Hoffer, Mariëtte JV, Reijnders, Margot RF, Demirdas, Serwet, Koboldt, Daniel C, Bartholomew, Dennis, Mosher, Theresa Mihalic, Hickey, Scott E, Shieh, Christine, Sanchez-Lara, Pedro A, Graham, John M, Tezcan, Kamer, Schaefer, GB, Danylchuk, Noelle R, Asamoah, Alexander, Jackson, Kelly E, Yachelevich, Naomi, Au, Margaret, Pérez-Jurado, Luis A, and Kleefstra, Tjitske
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Undiagnosed Diseases Network ,Animals ,Humans ,Mice ,Ubiquitin Thiolesterase ,Transforming Growth Factor beta ,Developmental Disabilities ,Signal Transduction ,Phenotype ,Female ,Male ,Haploinsufficiency ,Intellectual Disability ,Brain malformation ,Deubiquitylating enzyme ,Hippocampus ,Neurodevelopmental disorder ,TGFβ ,USP9X ,Congenital Structural Anomalies ,Genetics ,Neurosciences ,Pediatric ,Mental Health ,Behavioral and Social Science ,Brain Disorders ,Clinical Research ,2.1 Biological and endogenous factors ,Aetiology ,Neurological ,TGF beta ,Biological Sciences ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Psychiatry - Abstract
BackgroundThe X-chromosome gene USP9X encodes a deubiquitylating enzyme that has been associated with neurodevelopmental disorders primarily in female subjects. USP9X escapes X inactivation, and in female subjects de novo heterozygous copy number loss or truncating mutations cause haploinsufficiency culminating in a recognizable syndrome with intellectual disability and signature brain and congenital abnormalities. In contrast, the involvement of USP9X in male neurodevelopmental disorders remains tentative.MethodsWe used clinically recommended guidelines to collect and interrogate the pathogenicity of 44 USP9X variants associated with neurodevelopmental disorders in males. Functional studies in patient-derived cell lines and mice were used to determine mechanisms of pathology.ResultsTwelve missense variants showed strong evidence of pathogenicity. We define a characteristic phenotype of the central nervous system (white matter disturbances, thin corpus callosum, and widened ventricles); global delay with significant alteration of speech, language, and behavior; hypotonia; joint hypermobility; visual system defects; and other common congenital and dysmorphic features. Comparison of in silico and phenotypical features align additional variants of unknown significance with likely pathogenicity. In support of partial loss-of-function mechanisms, using patient-derived cell lines, we show loss of only specific USP9X substrates that regulate neurodevelopmental signaling pathways and a united defect in transforming growth factor β signaling. In addition, we find correlates of the male phenotype in Usp9x brain-specific knockout mice, and further resolve loss of hippocampal-dependent learning and memory.ConclusionsOur data demonstrate the involvement of USP9X variants in a distinctive neurodevelopmental and behavioral syndrome in male subjects and identify plausible mechanisms of pathogenesis centered on disrupted transforming growth factor β signaling and hippocampal function.
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- 2020
19. Bi-allelic variants in INTS11 are associated with a complex neurological disorder
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Acosta, Maria T., Adam, Margaret, Adams, David R., Alvey, Justin, Amendola, Laura, Andrews, Ashley, Ashley, Euan A., Azamian, Mahshid S., Bacino, Carlos A., Bademci, Guney, Balasubramanyam, Ashok, Baldridge, Dustin, Bale, Jim, Bamshad, Michael, Barbouth, Deborah, Bayrak-Toydemir, Pinar, Beck, Anita, Beggs, Alan H., Behrens, Edward, Bejerano, Gill, Bellen, Hugo J., Bennet, Jimmy, Berg-Rood, Beverly, Bernstein, Jonathan A., Berry, Gerard T., Bican, Anna, Bivona, Stephanie, Blue, Elizabeth, Bohnsack, John, Bonner, Devon, Botto, Lorenzo, Boyd, Brenna, Briere, Lauren C., Brokamp, Elly, Brown, Gabrielle, Burke, Elizabeth A., Burrage, Lindsay C., Butte, Manish J., Byers, Peter, Byrd, William E., Carey, John, Carrasquillo, Olveen, Cassini, Thomas, Peter Chang, Ta Chen, Chanprasert, Sirisak, Chao, Hsiao-Tuan, Clark, Gary D., Coakley, Terra R., Cobban, Laurel A., Cogan, Joy D., Coggins, Matthew, Cole, F. Sessions, Colley, Heather A., Cooper, Cynthia M., Cope, Heidi, Craigen, William J., Crouse, Andrew B., Cunningham, Michael, D'Souza, Precilla, Dai, Hongzheng, Dasari, Surendra, Davis, Joie, Dayal, Jyoti G., Deardorff, Matthew, Dell'Angelica, Esteban C., Dipple, Katrina, Doherty, Daniel, Dorrani, Naghmeh, Doss, Argenia L., Douine, Emilie D., Duncan, Laura, Earl, Dawn, Eckstein, David J., Emrick, Lisa T., Eng, Christine M., Esteves, Cecilia, Falk, Marni, Fernandez, Liliana, Fieg, Elizabeth L., Fisher, Paul G., Fogel, Brent L., Forghani, Irman, Gahl, William A., Glass, Ian, Gochuico, Bernadette, Godfrey, Rena A., Golden-Grant, Katie, Goldrich, Madison P., Grajewski, Alana, Gutierrez, Irma, Hadley, Don, Hahn, Sihoun, Hamid, Rizwan, Hassey, Kelly, Hayes, Nichole, High, Frances, Hing, Anne, Hisama, Fuki M., Holm, Ingrid A., Hom, Jason, Horike-Pyne, Martha, Huang, Alden, Huang, Yong, Introne, Wendy, Isasi, Rosario, Izumi, Kosuke, Jamal, Fariha, Jarvik, Gail P., Jarvik, Jeffrey, Jayadev, Suman, Jean-Marie, Orpa, Jobanputra, Vaidehi, Karaviti, Lefkothea, Kennedy, Jennifer, Ketkar, Shamika, Kiley, Dana, Kilich, Gonench, Kobren, Shilpa N., Kohane, Isaac S., Kohler, Jennefer N., Krakow, Deborah, Krasnewich, Donna M., Kravets, Elijah, Korrick, Susan, Koziura, Mary, Lalani, Seema R., Lam, Byron, Lam, Christina, LaMoure, Grace L., Lanpher, Brendan C., Lanza, Ian R., LeBlanc, Kimberly, Lee, Brendan H., Levitt, Roy, Lewis, Richard A., Liu, Pengfei, Liu, Xue Zhong, Longo, Nicola, Loo, Sandra K., Loscalzo, Joseph, Maas, Richard L., Macnamara, Ellen F., MacRae, Calum A., Maduro, Valerie V., Mahoney, Rachel, Mak, Bryan C., Malicdan, May Christine V., Mamounas, Laura A., Manolio, Teri A., Mao, Rong, Maravilla, Kenneth, Marom, Ronit, Marth, Gabor, Martin, Beth A., Martin, Martin G., Martínez-Agosto, Julian A., Marwaha, Shruti, McCauley, Jacob, McConkie-Rosell, Allyn, McCray, Alexa T., McGee, Elisabeth, Mefford, Heather, Merritt, J. Lawrence, Might, Matthew, Mirzaa, Ghayda, Morava, Eva, Moretti, Paolo M., Nakano-Okuno, Mariko, Nelson, Stan F., Newman, John H., Nicholas, Sarah K., Nickerson, Deborah, Nieves-Rodriguez, Shirley, Novacic, Donna, Oglesbee, Devin, Orengo, James P., Pace, Laura, Pak, Stephen, Pallais, J. Carl, Palmer, Christina GS., Papp, Jeanette C., Parker, Neil H., Phillips, John A., III, Posey, Jennifer E., Potocki, Lorraine, Pusey, Barbara N., Quinlan, Aaron, Raskind, Wendy, Raja, Archana N., Rao, Deepak A., Raper, Anna, Renteria, Genecee, Reuter, Chloe M., Rives, Lynette, Robertson, Amy K., Rodan, Lance H., Rosenfeld, Jill A., Rosenwasser, Natalie, Rossignol, Francis, Ruzhnikov, Maura, Sacco, Ralph, Sampson, Jacinda B., Saporta, Mario, Schaechter, Judy, Schedl, Timothy, Schoch, Kelly, Scott, C. Ron, Scott, Daryl A., Shashi, Vandana, Shin, Jimann, Silverman, Edwin K., Sinsheimer, Janet S., Sisco, Kathy, Smith, Edward C., Smith, Kevin S., Solem, Emily, Krezel, Lilianna Solnica, Solomon, Ben, Spillmann, Rebecca C., Stoler, Joan M., Sullivan, Jennifer A., Sullivan, Kathleen, Sun, Angela, Sutton, Shirley, Sweetser, David A., Sybert, Virginia, Tabor, Holly K., Tan, Amelia L.M., Tan, Queenie K.- G., Tekin, Mustafa, Telischi, Fred, Thorson, Willa, Tifft, Cynthia J., Toro, Camilo, Tran, Alyssa A., Tucker, Brianna M., Urv, Tiina K., Vanderver, Adeline, Velinder, Matt, Viskochil, Dave, Vogel, Tiphanie P., Wahl, Colleen E., Walker, Melissa, Wallace, Stephanie, Walley, Nicole M., Wambach, Jennifer, Wan, Jijun, Wang, Lee-kai, Wangler, Michael F., Ward, Patricia A., Wegner, Daniel, Weisz-Hubshman, Monika, Wener, Mark, Wenger, Tara, Perry, Katherine Wesseling, Westerfield, Monte, Wheeler, Matthew T., Whitlock, Jordan, Wolfe, Lynne A., Worley, Kim, Xiao, Changrui, Yamamoto, Shinya, Yang, John, Zastrow, Diane B., Zhang, Zhe, Zhao, Chunli, Zuchner, Stephan, Tepe, Burak, Macke, Erica L., Niceta, Marcello, Weisz Hubshman, Monika, Kanca, Oguz, Schultz-Rogers, Laura, Zarate, Yuri A., Schaefer, G. Bradley, Granadillo De Luque, Jorge Luis, Wegner, Daniel J., Cogne, Benjamin, Gilbert-Dussardier, Brigitte, Le Guillou, Xavier, Wagner, Eric J., Pais, Lynn S., Neil, Jennifer E., Mochida, Ganeshwaran H., Walsh, Christopher A., Magal, Nurit, Drasinover, Valerie, Shohat, Mordechai, Schwab, Tanya, Schmitz, Chris, Clark, Karl, Fine, Anthony, Lanpher, Brendan, Gavrilova, Ralitza, Blanc, Pierre, Burglen, Lydie, Afenjar, Alexandra, Steel, Dora, Kurian, Manju A., Prabhakar, Prab, Gößwein, Sophie, Di Donato, Nataliya, Bertini, Enrico S., Tartaglia, Marco, and Klee, Eric W.
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- 2023
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20. Genome-wide Analyses of Histone Modifications in the Mammalian Genome
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Tian, Shulan, primary, Slager, Susan L., additional, Klee, Eric W., additional, and Yan, Huihuang, additional
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- 2023
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21. List of contributors
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Akimitsu, Nobuyoshi, primary, Alexeeva, Marina, additional, Almeida, Juliana, additional, Ávila-Avilés, Rodolfo Daniel, additional, Berthelier, Jérémy, additional, Bhatnagar, Akanksha, additional, Boskovic, Maria, additional, Carullo, Nancy V.N., additional, Casas-Mollano, J. Armando, additional, Champagne, Frances A., additional, Chen, Taiping, additional, Chhabra, Ravindresh, additional, Curley, James P., additional, Davison, Gareth W., additional, Dunbar, Gary L., additional, Eggermann, Thomas, additional, Elefant, Felice, additional, Fransquet, Peter D., additional, Fujii, Hodaka, additional, Fujita, Toshitsugu, additional, Furci, Leonardo, additional, Garcia, Jose, additional, Ghosh, Balaram, additional, Gillberg, Linn, additional, Giménez-Orenga, Karen, additional, Hanna, Courtney W., additional, Herceg, Zdenko, additional, Hernández-Hernández, J. Manuel, additional, Hjort, Line, additional, Hu, Xiaotong, additional, Ibeagha-Awemu, Eveline M., additional, Jawaid, Ali, additional, Jiang, Wei, additional, Juez, Oscar, additional, Karnay, Ashley M., additional, Kawata, Kentaro, additional, Khatib, Hasan, additional, Klee, Eric W., additional, Klein, Kerstin, additional, Kremer, Eloïse A., additional, Kronholm, Ilkka, additional, Lee, Ho-Sun, additional, Magdinier, Frédérique, additional, Mansuy, Isabelle M., additional, Mashoodh, Rahia, additional, Mezei, Mihaly, additional, Miah, Maria, additional, Miryeganeh, Matin, additional, Mujtaba, Shiraz, additional, Munster, Pamela N., additional, Murr, Rabih, additional, Navakauskienė, Rūta, additional, Negrón-Lomas, Claudia, additional, Nugent, Fereshteh S., additional, Oltra, Elisa, additional, Onoguchi-Mizutani, Rena, additional, Öztürk, Nail Can, additional, Pacaud, Romain, additional, Peedicayil, Jacob, additional, Pethe, Prasad, additional, Pfeifer, Gerd P., additional, Pulya, Sravani, additional, Rauch, Tibor A., additional, Resendiz, Marisol, additional, Roalsø, Marcus, additional, Robin, Jérôme D., additional, Rossignol, Julien, additional, Ryan, Joanne, additional, Santos-Rebouças, Cíntia Barros, additional, Saze, Hidetoshi, additional, Shepard, Ryan D., additional, Silar, Philippe, additional, Sklias, Athena, additional, Slager, Susan L., additional, Søreide, Kjetil, additional, Srinageshwar, Bhairavi, additional, Suter, David M., additional, Taniue, Kenzui, additional, Thomas, Scott, additional, Tian, Shulan, additional, Tollefsbol, Trygve O., additional, van der Giezen, Mark, additional, Vanzan, Ludovica, additional, Vogt, Günter, additional, Watkins, Darryl S., additional, Watson, Martin M., additional, Wei, Loo Keat, additional, Wrigglesworth, Jo, additional, Yamada, Toshimichi, additional, Yan, Huihuang, additional, Yang, Jie, additional, Ying, Zhengzhou, additional, Zacarias, Ericka, additional, and Zhou, Feng C., additional
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- 2023
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22. Further clinical and molecular characterization of an XLID syndrome associated with BRWD3 variants, a gene implicated in the leukemia-related JAK-STAT pathway
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Delanne, Julian, Lecat, Magaly, Blackburn, Patrick R., Klee, Eric W., Stumpel, Constance T.R.M., Stegmann, Sander, Stevens, Servi J.C., Nava, Caroline, Heron, Delphine, Keren, Boris, Mahida, Sonal, Naidu, Sakkubai, Babovic-Vuksanovic, Dusica, Herkert, Johanna C., Torring, Pernille M., Kibæk, Maria, De Bie, Isabelle, Pfundt, Rolph, Hendriks, Yvonne M.C., Ousager, Lilian Bomme, Bend, Renee, Warren, Hannah, Skinner, Steven A., Lyons, Michael J., Pöe, Charlotte, Chevarin, Martin, Jouan, Thibaud, Garde, Aurore, Thomas, Quentin, Kuentz, Paul, Tisserant, Emilie, Duffourd, Yannis, Philippe, Christophe, Faivre, Laurence, and Thauvin-Robinet, Christel
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- 2023
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23. Clonal dynamics of Richter transformation in chronic lymphocytic leukemia
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Wang, Hanyin, primary, Tian, Shulan, additional, Secreto, Charla R., additional, Sinha, Sutapa, additional, Shi, Min, additional, Call, Timothy, additional, Wang, Yucai, additional, Parikh, Sameer A., additional, Kenderian, Saad S., additional, He, Rong, additional, Leis, Jose F., additional, VanDyke, Daniel L., additional, Klee, Eric W., additional, Slager, Susan L., additional, Braggio, Esteban, additional, Yan, Huihuang, additional, and Ding, Wei, additional
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- 2024
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24. The expanding clinical and genetic spectrum of DYNC1H1-related disorders
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Möller, Birk, primary, Becker, Lena-Luise, additional, Saffari, Afshin, additional, Afenjar, Alexandra, additional, Coci, Emanuele G, additional, Williamson, Rachel, additional, Ward-Melver, Catherine, additional, Gibaud, Marc, additional, Sedláčková, Lucie, additional, Laššuthová, Petra, additional, Libá, Zuzana, additional, Vlčková, Markéta, additional, William, Nancy, additional, Klee, Eric W, additional, Gavrilova, Ralitza H, additional, Lévy, Jonathan, additional, Capri, Yline, additional, Scavina, Mena, additional, Körner, Robert Walter, additional, Valuvullah, Zaheer, additional, Weiß, Claudia, additional, Möller, Greta Marit, additional, Thiel, Moritz, additional, Sinnema, Margje, additional, Kamsteeg, Erik-Jan, additional, Donkervoort, Sandra, additional, Duboc, Veronique, additional, Zaafrane-Khachnaoui, Khaoula, additional, Elkhateeb, Nour, additional, Selim, Laila, additional, Margot, Henri, additional, Marin, Victor, additional, Beneteau, Claire, additional, Isidor, Bertrand, additional, Cogne, Benjamin, additional, Keren, Boris, additional, Küsters, Benno, additional, Beggs, Alan H, additional, Genetti, Casie A, additional, Nicolai, Joost, additional, Dötsch, Jörg, additional, Koy, Anne, additional, Bönnemann, Carsten G, additional, von der Hagen, Maja, additional, von Kleist-Retzow, Jürgen-Christoph, additional, Voermans, Nicol, additional, Jungbluth, Heinz, additional, and Dafsari, Hormos Salimi, additional
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- 2024
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25. Interpretation of Dihydrorhodamine-1,2,3 Flow Cytometry in Chronic Granulomatous Disease: an Atypical Exemplar
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Donko, Agnes, Kuhns, Douglas B., Cousin, Margot A., Smith, Matthew J., Sacco, Keith A., Klee, Eric W., Joshi, Avni Y., Gavrilova, Ralitza H., Holland, Steven M., Leto, Thomas L., and Abraham, Roshini S.
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- 2022
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26. Missense Variants in the Histone Acetyltransferase Complex Component Gene TRRAP Cause Autism and Syndromic Intellectual Disability.
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Cogné, Benjamin, Ehresmann, Sophie, Beauregard-Lacroix, Eliane, Rousseau, Justine, Besnard, Thomas, Garcia, Thomas, Petrovski, Slavé, Avni, Shiri, McWalter, Kirsty, Blackburn, Patrick R, Sanders, Stephan J, Uguen, Kévin, Harris, Jacqueline, Cohen, Julie S, Blyth, Moira, Lehman, Anna, Berg, Jonathan, Li, Mindy H, Kini, Usha, Joss, Shelagh, von der Lippe, Charlotte, Gordon, Christopher T, Humberson, Jennifer B, Robak, Laurie, Scott, Daryl A, Sutton, Vernon R, Skraban, Cara M, Johnston, Jennifer J, Poduri, Annapurna, Nordenskjöld, Magnus, Shashi, Vandana, Gerkes, Erica H, Bongers, Ernie MHF, Gilissen, Christian, Zarate, Yuri A, Kvarnung, Malin, Lally, Kevin P, Kulch, Peggy A, Daniels, Brina, Hernandez-Garcia, Andres, Stong, Nicholas, McGaughran, Julie, Retterer, Kyle, Tveten, Kristian, Sullivan, Jennifer, Geisheker, Madeleine R, Stray-Pedersen, Asbjorg, Tarpinian, Jennifer M, Klee, Eric W, Sapp, Julie C, Zyskind, Jacob, Holla, Øystein L, Bedoukian, Emma, Filippini, Francesca, Guimier, Anne, Picard, Arnaud, Busk, Øyvind L, Punetha, Jaya, Pfundt, Rolph, Lindstrand, Anna, Nordgren, Ann, Kalb, Fayth, Desai, Megha, Ebanks, Ashley Harmon, Jhangiani, Shalini N, Dewan, Tammie, Coban Akdemir, Zeynep H, Telegrafi, Aida, Zackai, Elaine H, Begtrup, Amber, Song, Xiaofei, Toutain, Annick, Wentzensen, Ingrid M, Odent, Sylvie, Bonneau, Dominique, Latypova, Xénia, Deb, Wallid, CAUSES Study, Redon, Sylvia, Bilan, Frédéric, Legendre, Marine, Troyer, Caitlin, Whitlock, Kerri, Caluseriu, Oana, Murphree, Marine I, Pichurin, Pavel N, Agre, Katherine, Gavrilova, Ralitza, Rinne, Tuula, Park, Meredith, Shain, Catherine, Heinzen, Erin L, Xiao, Rui, Amiel, Jeanne, Lyonnet, Stanislas, Isidor, Bertrand, Biesecker, Leslie G, Lowenstein, Dan, Posey, Jennifer E, and Denommé-Pichon, Anne-Sophie
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CAUSES Study ,Deciphering Developmental Disorders study ,Humans ,Syndrome ,Adaptor Proteins ,Signal Transducing ,Nuclear Proteins ,Prognosis ,Autistic Disorder ,Amino Acid Sequence ,Sequence Homology ,Mutation ,Missense ,Adolescent ,Adult ,Child ,Child ,Preschool ,Infant ,Female ,Male ,Young Adult ,Genetic Association Studies ,Intellectual Disability ,TRRAP ,autism spectrum disorder ,congenital malformations ,de novo variants ,histone acetylation ,intellectual disability ,neurodevelopmental disorders ,Intellectual and Developmental Disabilities (IDD) ,Pediatric ,Genetics ,Brain Disorders ,Neurosciences ,Mental Health ,Autism ,Rare Diseases ,2.1 Biological and endogenous factors ,Aetiology ,Mental health ,Biological Sciences ,Medical and Health Sciences ,Genetics & Heredity - Abstract
Acetylation of the lysine residues in histones and other DNA-binding proteins plays a major role in regulation of eukaryotic gene expression. This process is controlled by histone acetyltransferases (HATs/KATs) found in multiprotein complexes that are recruited to chromatin by the scaffolding subunit transformation/transcription domain-associated protein (TRRAP). TRRAP is evolutionarily conserved and is among the top five genes intolerant to missense variation. Through an international collaboration, 17 distinct de novo or apparently de novo variants were identified in TRRAP in 24 individuals. A strong genotype-phenotype correlation was observed with two distinct clinical spectra. The first is a complex, multi-systemic syndrome associated with various malformations of the brain, heart, kidneys, and genitourinary system and characterized by a wide range of intellectual functioning; a number of affected individuals have intellectual disability (ID) and markedly impaired basic life functions. Individuals with this phenotype had missense variants clustering around the c.3127G>A p.(Ala1043Thr) variant identified in five individuals. The second spectrum manifested with autism spectrum disorder (ASD) and/or ID and epilepsy. Facial dysmorphism was seen in both groups and included upslanted palpebral fissures, epicanthus, telecanthus, a wide nasal bridge and ridge, a broad and smooth philtrum, and a thin upper lip. RNA sequencing analysis of skin fibroblasts derived from affected individuals skin fibroblasts showed significant changes in the expression of several genes implicated in neuronal function and ion transport. Thus, we describe here the clinical spectrum associated with TRRAP pathogenic missense variants, and we suggest a genotype-phenotype correlation useful for clinical evaluation of the pathogenicity of the variants.
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- 2019
27. Exome sequencing can misread high variant allele fraction of somatic variants in UBA1 as hemizygous in VEXAS syndrome: a case report
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Wilke, Matheus V. M. B., Morava-Kozicz, Eva, Koster, Matthew J., Schmitz, Christopher T., Foster, Shannon Kaye, Patnaik, Mrinal, Warrington, Kenneth J., Klee, Eric W., and Pinto e Vairo, Filippo
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- 2022
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28. Gain and loss of TASK3 channel function and its regulation by novel variation cause KCNK9 imprinting syndrome
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Cousin, Margot A., Veale, Emma L., Dsouza, Nikita R., Tripathi, Swarnendu, Holden, Robyn G., Arelin, Maria, Beek, Geoffrey, Bekheirnia, Mir Reza, Beygo, Jasmin, Bhambhani, Vikas, Bialer, Martin, Bigoni, Stefania, Boelman, Cyrus, Carmichael, Jenny, Courtin, Thomas, Cogne, Benjamin, Dabaj, Ivana, Doummar, Diane, Fazilleau, Laura, Ferlini, Alessandra, Gavrilova, Ralitza H., Graham, Jr, John M., Haack, Tobias B., Juusola, Jane, Kant, Sarina G., Kayani, Saima, Keren, Boris, Ketteler, Petra, Klöckner, Chiara, Koopmann, Tamara T., Kruisselbrink, Teresa M., Kuechler, Alma, Lambert, Laëtitia, Latypova, Xénia, Lebel, Robert Roger, Leduc, Magalie S., Leonardi, Emanuela, Lewis, Andrea M., Liew, Wendy, Machol, Keren, Mardini, Samir, McWalter, Kirsty, Mignot, Cyril, McLaughlin, Julie, Murgia, Alessandra, Narayanan, Vinodh, Nava, Caroline, Neuser, Sonja, Nizon, Mathilde, Ognibene, Davide, Park, Joohyun, Platzer, Konrad, Poirsier, Céline, Radtke, Maximilian, Ramsey, Keri, Runke, Cassandra K., Guillen Sacoto, Maria J., Scaglia, Fernando, Shinawi, Marwan, Spranger, Stephanie, Tan, Ee Shien, Taylor, John, Trentesaux, Anne-Sophie, Vairo, Filippo, Willaert, Rebecca, Zadeh, Neda, Urrutia, Raul, Babovic-Vuksanovic, Dusica, Zimmermann, Michael T., Mathie, Alistair, and Klee, Eric W.
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- 2022
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29. De Novo Pathogenic Variants in CACNA1E Cause Developmental and Epileptic Encephalopathy with Contractures, Macrocephaly, and Dyskinesias
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Helbig, Katherine L, Lauerer, Robert J, Bahr, Jacqueline C, Souza, Ivana A, Myers, Candace T, Uysal, Betül, Schwarz, Niklas, Gandini, Maria A, Huang, Sun, Keren, Boris, Mignot, Cyril, Afenjar, Alexandra, de Villemeur, Thierry Billette, Héron, Delphine, Nava, Caroline, Valence, Stéphanie, Buratti, Julien, Fagerberg, Christina R, Soerensen, Kristina P, Kibaek, Maria, Kamsteeg, Erik-Jan, Koolen, David A, Gunning, Boudewijn, Schelhaas, H Jurgen, Kruer, Michael C, Fox, Jordana, Bakhtiari, Somayeh, Jarrar, Randa, Padilla-Lopez, Sergio, Lindstrom, Kristin, Jin, Sheng Chih, Zeng, Xue, Bilguvar, Kaya, Papavasileiou, Antigone, Xing, Qinghe, Zhu, Changlian, Boysen, Katja, Vairo, Filippo, Lanpher, Brendan C, Klee, Eric W, Tillema, Jan-Mendelt, Payne, Eric T, Cousin, Margot A, Kruisselbrink, Teresa M, Wick, Myra J, Baker, Joshua, Haan, Eric, Smith, Nicholas, Sadeghpour, Azita, Davis, Erica E, Katsanis, Nicholas, Genomics, Task Force for Neonatal, Allori, Alexander, Angrist, Misha, Ashley, Patricia, Bidegain, Margarita, Boyd, Brita, Chambers, Eileen, Cope, Heidi, Cotten, C Michael, Curington, Theresa, Ellestad, Sarah, Fisher, Kimberley, French, Amanda, Gallentine, William, Goldberg, Ronald, Hill, Kevin, Kansagra, Sujay, Katsanis, Sara, Kurtzberg, Joanne, Marcus, Jeffrey, McDonald, Marie, Mikati, Mohammed, Miller, Stephen, Murtha, Amy, Perilla, Yezmin, Pizoli, Carolyn, Purves, Todd, Ross, Sherry, Smith, Edward, Wiener, John, Corbett, Mark A, MacLennan, Alastair H, Gecz, Jozef, Biskup, Saskia, Goldmann, Eva, Rodan, Lance H, Kichula, Elizabeth, Segal, Eric, Jackson, Kelly E, Asamoah, Alexander, Dimmock, David, McCarrier, Julie, Botto, Lorenzo D, Filloux, Francis, Tvrdik, Tatiana, and Cascino, Gregory D
- Subjects
Medical Physiology ,Biomedical and Clinical Sciences ,Neurodegenerative ,Brain Disorders ,Neurosciences ,Epilepsy ,Pediatric ,2.1 Biological and endogenous factors ,Aetiology ,Neurological ,Adolescent ,Adult ,Calcium Channels ,R-Type ,Cation Transport Proteins ,Child ,Child ,Preschool ,Contracture ,Dyskinesias ,Female ,Genetic Variation ,Humans ,Infant ,Male ,Megalencephaly ,Neurodevelopmental Disorders ,Spasms ,Infantile ,Task Force for Neonatal Genomics ,Deciphering Developmental Disorders Study ,CACNA1E ,ion channel ,arthrogryposis ,calcium channel ,epilepsy ,Biological Sciences ,Medical and Health Sciences ,Genetics & Heredity ,Biological sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
Developmental and epileptic encephalopathies (DEEs) are severe neurodevelopmental disorders often beginning in infancy or early childhood that are characterized by intractable seizures, abundant epileptiform activity on EEG, and developmental impairment or regression. CACNA1E is highly expressed in the central nervous system and encodes the α1-subunit of the voltage-gated CaV2.3 channel, which conducts high voltage-activated R-type calcium currents that initiate synaptic transmission. Using next-generation sequencing techniques, we identified de novo CACNA1E variants in 30 individuals with DEE, characterized by refractory infantile-onset seizures, severe hypotonia, and profound developmental impairment, often with congenital contractures, macrocephaly, hyperkinetic movement disorders, and early death. Most of the 14, partially recurring, variants cluster within the cytoplasmic ends of all four S6 segments, which form the presumed CaV2.3 channel activation gate. Functional analysis of several S6 variants revealed consistent gain-of-function effects comprising facilitated voltage-dependent activation and slowed inactivation. Another variant located in the domain II S4-S5 linker results in facilitated activation and increased current density. Five participants achieved seizure freedom on the anti-epileptic drug topiramate, which blocks R-type calcium channels. We establish pathogenic variants in CACNA1E as a cause of DEEs and suggest facilitated R-type calcium currents as a disease mechanism for human epilepsy and developmental disorders.
- Published
- 2018
30. Unified somatic calling and machine learning-based classification enhance the discovery of clonal hematopoiesis of indeterminate potential
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Tian, Shulan, primary, Ferrer, Alejandro, additional, Yan, Huihuang, additional, Morales-Rosado, Joel, additional, Lasho, Terro L, additional, Wang, Kevin, additional, Baheti, Saurabh, additional, Olson, Janet E, additional, Baughn, Linda B, additional, Slager, Susan L, additional, Patnaik, Mrinal M., additional, Lazaridis, Konstantinos N, additional, and Klee, Eric W, additional
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- 2024
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31. MARK2 variants cause autism spectrum disorder via the downregulation of WNT/β-catenin signaling pathway
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Gong, Maolei, primary, Li, Jiayi, additional, Liu, Yijun, additional, Matheus, Vernet Machado Bressan Wilk, additional, Li, Qian, additional, Liu, Haoran, additional, Liang, Chen, additional, Joel A, Morales-Rosado, additional, Cohen, Ana S.A., additional, Hughes, Susan S., additional, Sullivan, Bonnie R, additional, Waddell, Valerie, additional, Henriette van den Boogaard, Marie Jose, additional, van Jaarsveld, Richard H., additional, Binsbergen, Ellen van, additional, van Gassen, Koen L, additional, Wang, Tianyun, additional, Hiatt, Susan M., additional, Amaral, Michelle D., additional, Kelley, Whitley V., additional, Zhao, Jianbo, additional, Feng, Weixing, additional, Ren, Changhong, additional, Yu, Yazhen, additional, Boczek, Nicole J, additional, Ferber, Matthew J., additional, Lahner, Carrie, additional, Elliott, Sherr, additional, Ruan, Yiyan, additional, Mignot, Cyril, additional, Keren, Boris, additional, Xie, Hua, additional, Wang, Xiaoyan, additional, Popp, Bernt, additional, Zweier, Christiane, additional, Piard, Juliette, additional, Coubes, Christine, additional, Tran-Mau-Them, Frederic, additional, Safraou, Hana, additional, Innes, Micheil, additional, Gauthier, Julie, additional, Michaud, Jacques L, additional, Koboldt, Daniel C., additional, Sylvie, ODENT, additional, Willems, Marjolaine, additional, Tan, Wen-Hann, additional, Cogne, Benjamin, additional, Rieubland, Claudine, additional, Braun, Dominique, additional, McLean, Scott Douglas, additional, Platzer, Konrad, additional, Zacher, Pia, additional, Oppermann, Henry, additional, Evenepoel, Lucie, additional, BLANC, Pierre, additional, Khattabi, Laila El, additional, Haque, Neshatul, additional, Dsouza, Nikita R., additional, Zimmermann, Michael T, additional, Urrutia, Raul A, additional, Klee, Eric W, additional, Shen, Yiping, additional, Du, Hong-Zhen, additional, Qin, Zailong, additional, Liu, Chang-Mei, additional, and chen, xiaoli, additional
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- 2024
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32. OmicsFootPrint: a framework to integrate and interpret multi-omics data using circular images and deep neural networks
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Tang, Xiaojia, primary, Prodduturi, Naresh, additional, Thompson, Kevin J., additional, Weinshilboum, Richard, additional, O’Sullivan, Ciara C., additional, Boughey, Judy C., additional, Tizhoosh, Hamid R., additional, Klee, Eric W., additional, Wang, Liewei, additional, Goetz, Matthew P., additional, Suman, Vera, additional, and Kalari, Krishna R., additional
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- 2024
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33. Genomics Integration Into Nephrology Practice
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Pinto e Vairo, Filippo, Prochnow, Carri, Kemppainen, Jennifer L., Lisi, Emily C., Steyermark, Joan M., Kruisselbrink, Teresa M., Pichurin, Pavel N., Dhamija, Rhadika, Hager, Megan M., Albadri, Sam, Cornell, Lynn D., Lazaridis, Konstantinos N., Klee, Eric W., Senum, Sarah R., El Ters, Mireille, Amer, Hatem, Baudhuin, Linnea M., Moyer, Ann M., Keddis, Mira T., Zand, Ladan, Sas, David J., Erickson, Stephen B., Fervenza, Fernando C., Lieske, John C., Harris, Peter C., and Hogan, Marie C.
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- 2021
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34. One in seven pathogenic variants can be challenging to detect by NGS: an analysis of 450,000 patients with implications for clinical sensitivity and genetic test implementation
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Lincoln, Stephen E., Hambuch, Tina, Zook, Justin M., Bristow, Sara L., Hatchell, Kathryn, Truty, Rebecca, Kennemer, Michael, Shirts, Brian H., Fellowes, Andrew, Chowdhury, Shimul, Klee, Eric W., Mahamdallie, Shazia, Cleveland, Megan H., Vallone, Peter M., Ding, Yan, Seal, Sheila, DeSilva, Wasanthi, Tomson, Farol L., Huang, Catherine, Garlick, Russell K., Rahman, Nazneen, Salit, Marc, Kingsmore, Stephen F., Ferber, Matthew J., Aradhya, Swaroop, and Nussbaum, Robert L.
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- 2021
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35. Pathogenic SPTBN1 variants cause an autosomal dominant neurodevelopmental syndrome
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Cousin, Margot A., Creighton, Blake A., Breau, Keith A., Spillmann, Rebecca C., Torti, Erin, Dontu, Sruthi, Tripathi, Swarnendu, Ajit, Deepa, Edwards, Reginald J., Afriyie, Simone, Bay, Julia C., Harper, Kathryn M., Beltran, Alvaro A., Munoz, Lorena J., Falcon Rodriguez, Liset, Stankewich, Michael C., Person, Richard E., Si, Yue, Normand, Elizabeth A., Blevins, Amy, May, Alison S., Bier, Louise, Aggarwal, Vimla, Mancini, Grazia M. S., van Slegtenhorst, Marjon A., Cremer, Kirsten, Becker, Jessica, Engels, Hartmut, Aretz, Stefan, MacKenzie, Jennifer J., Brilstra, Eva, van Gassen, Koen L. I., van Jaarsveld, Richard H., Oegema, Renske, Parsons, Gretchen M., Mark, Paul, Helbig, Ingo, McKeown, Sarah E., Stratton, Robert, Cogne, Benjamin, Isidor, Bertrand, Cacheiro, Pilar, Smedley, Damian, Firth, Helen V., Bierhals, Tatjana, Kloth, Katja, Weiss, Deike, Fairley, Cecilia, Shieh, Joseph T., Kritzer, Amy, Jayakar, Parul, Kurtz-Nelson, Evangeline, Bernier, Raphael A., Wang, Tianyun, Eichler, Evan E., van de Laar, Ingrid M. B. H., McConkie-Rosell, Allyn, McDonald, Marie T., Kemppainen, Jennifer, Lanpher, Brendan C., Schultz-Rogers, Laura E., Gunderson, Lauren B., Pichurin, Pavel N., Yoon, Grace, Zech, Michael, Jech, Robert, Winkelmann, Juliane, Beltran, Adriana S., Zimmermann, Michael T., Temple, Brenda, Moy, Sheryl S., Klee, Eric W., Tan, Queenie K.-G., and Lorenzo, Damaris N.
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- 2021
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36. Next-Generation Sequencing of CYP2C19 in Stent Thrombosis: Implications for Clopidogrel Pharmacogenomics
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Morales-Rosado, Joel A., Goel, Kashish, Zhang, Lingxin, Åkerblom, Axel, Baheti, Saurabh, Black, John L., Eriksson, Niclas, Wallentin, Lars, James, Stefan, Storey, Robert F., Goodman, Shaun G., Jenkins, Gregory D., Eckloff, Bruce W., Bielinski, Suzette J., Sicotte, Hugues, Johnson, Stephen, Roger, Veronique L., Wang, Liewei, Weinshilboum, Richard, Klee, Eric W., Rihal, Charanjit S., and Pereira, Naveen L.
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- 2021
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37. A Genotype/Phenotype Study of KDM5B-Associated Disorders Suggests a Pathogenic Effect of Dominantly Inherited Missense Variants
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Genetica, Genetica Klinische Genetica, Child Health, Borroto, Maria Carla, Michaud, Coralie, Hudon, Chloé, Agrawal, Pankaj B., Agre, Katherine, Applegate, Carolyn D., Beggs, Alan H., Bjornsson, Hans T., Callewaert, Bert, Chen, Mei Jan, Curry, Cynthia, Devinsky, Orrin, Dudding-Byth, Tracy, Fagan, Kelly, Finnila, Candice R., Gavrilova, Ralitza, Genetti, Casie A., Hiatt, Susan M., Hildebrandt, Friedhelm, Wojcik, Monica H., Kleefstra, Tjitske, Kolvenbach, Caroline M., Korf, Bruce R., Kruszka, Paul, Li, Hong, Litwin, Jessica, Marcadier, Julien, Platzer, Konrad, Blackburn, Patrick R., Reijnders, Margot R.F., Reutter, Heiko, Schanze, Ina, Shieh, Joseph T., Stevens, Cathy A., Valivullah, Zaheer, van den Boogaard, Marie José, Klee, Eric W., Campeau, Philippe M., Genetica, Genetica Klinische Genetica, Child Health, Borroto, Maria Carla, Michaud, Coralie, Hudon, Chloé, Agrawal, Pankaj B., Agre, Katherine, Applegate, Carolyn D., Beggs, Alan H., Bjornsson, Hans T., Callewaert, Bert, Chen, Mei Jan, Curry, Cynthia, Devinsky, Orrin, Dudding-Byth, Tracy, Fagan, Kelly, Finnila, Candice R., Gavrilova, Ralitza, Genetti, Casie A., Hiatt, Susan M., Hildebrandt, Friedhelm, Wojcik, Monica H., Kleefstra, Tjitske, Kolvenbach, Caroline M., Korf, Bruce R., Kruszka, Paul, Li, Hong, Litwin, Jessica, Marcadier, Julien, Platzer, Konrad, Blackburn, Patrick R., Reijnders, Margot R.F., Reutter, Heiko, Schanze, Ina, Shieh, Joseph T., Stevens, Cathy A., Valivullah, Zaheer, van den Boogaard, Marie José, Klee, Eric W., and Campeau, Philippe M.
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- 2024
38. Bi-allelic variants in CELSR3 are implicated in central nervous system and urinary tract anomalies
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Stegmann, Jil D, Kalanithy, Jeshurun C, Dworschak, Gabriel C, Ishorst, Nina, Mingardo, Enrico, Lopes, Filipa M, Ho, Yee Mang, Grote, Phillip, Lindenberg, Tobias T, Yilmaz, Öznur, Channab, Khadija, Seltzsam, Steve, Shril, Shirlee, Hildebrandt, Friedhelm, Boschann, Felix, Heinen, André, Jolly, Angad, Myers, Katherine, McBride, Kim, Bekheirnia, Mir Reza, Bekheirnia, Nasim, Scala, Marcello, Morleo, Manuela, Nigro, Vincenzo, Torella, Annalaura, Pinelli, Michele, Capra, Valeria, Accogli, Andrea, Maitz, Silvia, Spano, Alice, Olson, Rory J, Klee, Eric W, Lanpher, Brendan C, Jang, Se Song, Chae, Jong-Hee, Steinbauer, Philipp, Rieder, Dietmar, Janecke, Andreas R, Vodopiutz, Julia, Vogel, Ida, Blechingberg, Jenny, Cohen, Jennifer L, Riley, Kacie, Klee, Victoria, Walsh, Laurence E, Begemann, Matthias, Elbracht, Miriam, Eggermann, Thomas, Stuurman, Kyra, van Slegtenhorst, Marjon, Stegmann, Jil D, Kalanithy, Jeshurun C, Dworschak, Gabriel C, Ishorst, Nina, Mingardo, Enrico, Lopes, Filipa M, Ho, Yee Mang, Grote, Phillip, Lindenberg, Tobias T, Yilmaz, Öznur, Channab, Khadija, Seltzsam, Steve, Shril, Shirlee, Hildebrandt, Friedhelm, Boschann, Felix, Heinen, André, Jolly, Angad, Myers, Katherine, McBride, Kim, Bekheirnia, Mir Reza, Bekheirnia, Nasim, Scala, Marcello, Morleo, Manuela, Nigro, Vincenzo, Torella, Annalaura, Pinelli, Michele, Capra, Valeria, Accogli, Andrea, Maitz, Silvia, Spano, Alice, Olson, Rory J, Klee, Eric W, Lanpher, Brendan C, Jang, Se Song, Chae, Jong-Hee, Steinbauer, Philipp, Rieder, Dietmar, Janecke, Andreas R, Vodopiutz, Julia, Vogel, Ida, Blechingberg, Jenny, Cohen, Jennifer L, Riley, Kacie, Klee, Victoria, Walsh, Laurence E, Begemann, Matthias, Elbracht, Miriam, Eggermann, Thomas, Stuurman, Kyra, and van Slegtenhorst, Marjon
- Abstract
CELSR3 codes for a planar cell polarity protein. We describe twelve affected individuals from eleven independent families with bi-allelic variants in CELSR3. Affected individuals presented with an overlapping phenotypic spectrum comprising central nervous system (CNS) anomalies (7/12), combined CNS anomalies and congenital anomalies of the kidneys and urinary tract (CAKUT) (3/12) and CAKUT only (2/12). Computational simulation of the 3D protein structure suggests the position of the identified variants to be implicated in penetrance and phenotype expression. CELSR3 immunolocalization in human embryonic urinary tract and transient suppression and rescue experiments of Celsr3 in fluorescent zebrafish reporter lines further support an embryonic role of CELSR3 in CNS and urinary tract formation.
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- 2024
39. Impact of integrated translational research on clinical exome sequencing
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Klee, Eric W., Cousin, Margot A., Pinto e Vairo, Filippo, Morales-Rosado, Joel A., Macke, Erica L., Jenkinson, W. Garrett, Ferrer, Alejandro, Schultz-Rogers, Laura E., Olson, Rory J., Oliver, Gavin R., Sigafoos, Ashley N., Schwab, Tanya L., Zimmermann, Michael T., Urrutia, Raul A., Kaiwar, Charu, Gupta, Aditi, Blackburn, Patrick R., Boczek, Nicole J., Prochnow, Carri A., Lowy, Rebecca J., Mulvihill, Lindsay A., McAllister, Tammy M., Aoudia, Stacy L., Kruisselbrink, Teresa M., Gunderson, Lauren B., Kemppainen, Jennifer L., Fisher, Laura J., Tarnowski, Jessica M., Hager, Megan M., Kroc, Sarah A., Bertsch, Nicole L., Agre, Katherine E., Jackson, Jessica L., Macklin-Mantia, Sarah K., Murphree, Marine I., Rust, Laura M., Summer Bolster, Jolene M., Beck, Scott A., Atwal, Paldeep S., Ellingson, Marissa S., Barnett, Sarah S., Rasmussen, Kristen J., Lahner, Carrie A., Niu, Zhiyv, Hasadsri, Linda, Ferber, Matthew J., Marcou, Cherisse A., Clark, Karl J., Pichurin, Pavel N., Deyle, David R., Morava-Kozicz, Eva, Gavrilova, Ralitza H., Dhamija, Radhika, Wierenga, Klaas J., Lanpher, Brendan C., Babovic-Vuksanovic, Dusica, Farrugia, Gianrico, Schimmenti, Lisa A., Stewart, A. Keith, and Lazaridis, Konstantinos N.
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- 2021
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40. Genetic variants in DGAT1 cause diverse clinical presentations of malnutrition through a specific molecular mechanism
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Gupta, Aditi, Dsouza, Nikita R., Zarate, Yuri A., Lombardo, Rachel, Hopkin, Robert, Linehan, Allison R., Simpson, Jamela, McCarrier, Julie, Agre, Katherine E., Gavrilova, Ralitza H., Stephens, Michael C., Grothe, Rayna M., Monaghan, Kristin G., Xie, Yili, Basel, Donald, Urrutia, Raul A., Cole, Conrad R., Klee, Eric W., and Zimmermann, Michael T.
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- 2020
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41. Jumonji domain containing 1C (JMJD1C) sequence variants in seven patients with autism spectrum disorder, intellectual disability and seizures
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Slavotinek, Anne, van Hagen, Johanna M., Kalsner, Louisa, Pai, Shashidhar, Davis-Keppen, Laura, Ohden, Lisa, Weber, Yvonne G., Macke, Erica L., Klee, Eric W., Morava, Eva, Gunderson, Lauren, Person, Richard, Liu, Shuxi, and Weiss, Marjan
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- 2020
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42. Partial Loss of USP9X Function Leads to a Male Neurodevelopmental and Behavioral Disorder Converging on Transforming Growth Factor β Signaling
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Pena, Loren, Shashi, Vandana, Schoch, Kelly, Sullivan, Jennifer A., Acosta, Maria T., Adams, David R., Aday, Aaron, Alejandro, Mercedes E., Allard, Patrick, Ashley, Euan A., Azamian, Mahshid S., Bacino, Carlos A., Bademci, Guney, Baker, Eva, Balasubramanyam, Ashok, Baldridge, Dustin, Barbouth, Deborah, Batzli, Gabriel F., Beggs, Alan H., Bellen, Hugo J., Bernstein, Jonathan A., Berry, Gerard T., Bican, Anna, Bick, David P., Birch, Camille L., Bivona, Stephanie, Bonnenmann, Carsten, Bonner, Devon, Boone, Braden E., Bostwick, Bret L., Briere, Lauren C., Brokamp, Elly, Brown, Donna M., Brush, Matthew, Burke, Elizabeth A., Burrage, Lindsay C., Butte, Manish J., Carrasquillo, Olveen, Peter Chang, Ta Chen, Chao, Hsiao-Tuan, Clark, Gary D., Coakley, Terra R., Cobban, Laurel A., Cogan, Joy D., Cole, F. Sessions, Colley, Heather A., Cooper, Cynthia M., Cope, Heidi, Craigen, William J., D'Souza, Precilla, Dasari, Surendra, Davids, Mariska, Davidson, Jean M., Dayal, Jyoti G., Dell'Angelica, Esteban C., Dhar, Shweta U., Dorrani, Naghmeh, Dorset, Daniel C., Douine, Emilie D., Draper, David D., Dries, Annika M., Duncan, Laura, Eckstein, David J., Emrick, Lisa T., Eng, Christine M., Enns, Gregory M., Esteves, Cecilia, Estwick, Tyra, Fernandez, Liliana, Ferreira, Carlos, Fieg, Elizabeth L., Fisher, Paul G., Fogel, Brent L., Forghani, Irman, Friedman, Noah D., Gahl, William A., Godfrey, Rena A., Goldman, Alica M., Goldstein, David B., Gourdine, Jean-Philippe F., Grajewski, Alana, Groden, Catherine A., Gropman, Andrea L., Haendel, Melissa, Hamid, Rizwan, Hanchard, Neil A., High, Frances, Holm, Ingrid A., Hom, Jason, Huang, Alden, Huang, Yong, Isasi, Rosario, Jamal, Fariha, Jiang, Yong-hui, Johnston, Jean M., Jones, Angela L., Karaviti, Lefkothea, Kelley, Emily G., Koeller, David M., Kohane, Isaac S., Kohler, Jennefer N., Krakow, Deborah, Krasnewich, Donna M., Korrick, Susan, Koziura, Mary, Krier, Joel B., Kyle, Jennifer E., Lalani, Seema R., Lam, Byron, Lanpher, Brendan C., Lanza, Ian R., Lau, C. Christopher, Lazar, Jozef, LeBlanc, Kimberly, Lee, Brendan H., Lee, Hane, Levitt, Roy, Levy, Shawn E., Lewis, Richard A., Lincoln, Sharyn A., Liu, Pengfei, Liu, Xue Zhong, Loo, Sandra K., Loscalzo, Joseph, Maas, Richard L., Macnamara, Ellen F., MacRae, Calum A., Maduro, Valerie V., Majcherska, Marta M., Malicdan, May Christine V., Mamounas, Laura A., Manolio, Teri A., Markello, Thomas C., Marom, Ronit, Martin, Martin G., Martínez-Agosto, Julian A., Marwaha, Shruti, May, Thomas, McCauley, Jacob, McConkie-Rosell, Allyn, McCormack, Colleen E., McCray, Alexa T., Merker, Jason D., Metz, Thomas O., Might, Matthew, Morava-Kozicz, Eva, Moretti, Paolo M., Morimoto, Marie, Mulvihill, John J., Murdock, David R., Nath, Avi, Nelson, Stan F., Newberry, J. Scott, Newman, John H., Nicholas, Sarah K., Novacic, Donna, Oglesbee, Devin, Orengo, James P., Pak, Stephen, Pallais, J. Carl, Palmer, Christina GS., Papp, Jeanette C., Parker, Neil H., Phillips, John A., III, Posey, Jennifer E., Postlethwait, John H., Potocki, Lorraine, Pusey, Barbara N., Renteri, Genecee, Reuter, Chloe M., Rives, Lynette, Robertson, Amy K., Rodan, Lance H., Rosenfeld, Jill A., Rowley, Robb K., Sacco, Ralph, Sampson, Jacinda B., Samson, Susan L., Saporta, Mario, Schaechter, Judy, Schedl, Timothy, Scott, Daryl A., Shakachite, Lisa, Sharma, Prashant, Shields, Kathleen, Shin, Jimann, Signer, Rebecca, Sillari, Catherine H., Silverman, Edwin K., Sinsheimer, Janet S., Smith, Kevin S., Solnica-Krezel, Lilianna, Spillmann, Rebecca C., Stoler, Joan M., Stong, Nicholas, Sweetser, David A., Tamburro, Cecelia P., Tan, Queenie K.-G., Tekin, Mustafa, Telischi, Fred, Thorson, Willa, Tifft, Cynthia J., Toro, Camilo, Tran, Alyssa A., Urv, Tiina K., Vogel, Tiphanie P., Waggott, Daryl M., Wahl, Colleen E., Walley, Nicole M., Walsh, Chris A., Walker, Melissa, Wambach, Jennifer, Wan, Jijun, Wang, Lee-kai, Wangler, Michael F., Ward, Patricia A., Waters, Katrina M., Webb-Robertson, Bobbie-Jo M., Wegner, Daniel, Westerfield, Monte, Wheeler, Matthew T., Wise, Anastasia L., Wolfe, Lynne A., Woods, Jeremy D., Worthey, Elizabeth A., Yamamoto, Shinya, Yang, John, Yoon, Amanda J., Yu, Guoyun, Zastrow, Diane B., Zhao, Chunli, Zuchner, Stephan, Gahl, William, Johnson, Brett V., Kumar, Raman, Oishi, Sabrina, Alexander, Suzy, Kasherman, Maria, Vega, Michelle Sanchez, Ivancevic, Atma, Gardner, Alison, Domingo, Deepti, Corbett, Mark, Parnell, Euan, Yoon, Sehyoun, Oh, Tracey, Lines, Matthew, Lefroy, Henrietta, Kini, Usha, Van Allen, Margot, Grønborg, Sabine, Mercier, Sandra, Küry, Sébastien, Bézieau, Stéphane, Pasquier, Laurent, Raynaud, Martine, Afenjar, Alexandra, Billette de Villemeur, Thierry, Keren, Boris, Désir, Julie, Van Maldergem, Lionel, Marangoni, Martina, Dikow, Nicola, Koolen, David A., VanHasselt, Peter M., Weiss, Marjan, Zwijnenburg, Petra, Sa, Joaquim, Reis, Claudia Falcao, López-Otín, Carlos, Santiago-Fernández, Olaya, Fernández-Jaén, Alberto, Rauch, Anita, Steindl, Katharina, Joset, Pascal, Goldstein, Amy, Madan-Khetarpal, Suneeta, Infante, Elena, Zackai, Elaine, Mcdougall, Carey, Narayanan, Vinodh, Ramsey, Keri, Mercimek-Andrews, Saadet, Pinto e Vairo, Filippo, Pichurin, Pavel N., Ewing, Sarah A., Barnett, Sarah S., Klee, Eric W., Perry, M. Scott, Koenig, Mary Kay, Keegan, Catherine E., Schuette, Jane L., Asher, Stephanie, Perilla-Young, Yezmin, Smith, Laurie D., Bhoj, Elizabeth, Kaplan, Paige, Li, Dong, Oegema, Renske, van Binsbergen, Ellen, van der Zwaag, Bert, Smeland, Marie Falkenberg, Cutcutache, Ioana, Page, Matthew, Armstrong, Martin, Lin, Angela E., Steeves, Marcie A., Hollander, Nicolette den, Hoffer, Mariëtte J.V., Reijnders, Margot R.F., Demirdas, Serwet, Koboldt, Daniel C., Bartholomew, Dennis, Mosher, Theresa Mihalic, Hickey, Scott E., Shieh, Christine, Sanchez-Lara, Pedro A., Graham, John M., Jr., Tezcan, Kamer, Schaefer, G.B., Danylchuk, Noelle R., Asamoah, Alexander, Jackson, Kelly E., Yachelevich, Naomi, Au, Margaret, Pérez-Jurado, Luis A., Kleefstra, Tjitske, Penzes, Peter, Wood, Stephen A., Burne, Thomas, Pierson, Tyler Mark, Piper, Michael, Gécz, Jozef, and Jolly, Lachlan A.
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- 2020
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43. Nuclear Abnormalities in LMNA p.(Glu2Lys) Variant Segregating with LMNA-Associated Cardiocutaneous Progeria Syndrome
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Wilke, Matheus V. M. B., primary, Wick, Myra, additional, Schwab, Tanya L., additional, Starosta, Rodrigo Tzovenos, additional, Clark, Karl J., additional, Connolly, Heidi M., additional, and Klee, Eric W., additional
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- 2024
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44. Complex balanced intrachromosomal rearrangement involving PITX2 identified as a cause of Axenfeld‐Rieger Syndrome
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Farris, Joseph, primary, Khanna, Cheryl, additional, Smadbeck, James B., additional, Johnson, Sarah H., additional, Bothun, Erick, additional, Kaplan, Tyler, additional, Hoffman, Francis, additional, Polonis, Katarzyna, additional, Oliver, Gavin, additional, Reis, Linda M., additional, Semina, Elena V., additional, Rust, Laura, additional, Hoppman, Nicole L., additional, Vasmatzis, George, additional, Marcou, Cherisse A., additional, Schimmenti, Lisa A., additional, and Klee, Eric W., additional
- Published
- 2024
- Full Text
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45. Defining the genotypic and phenotypic spectrum of X-linked MSL3-related disorder
- Author
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Brunet, Theresa, McWalter, Kirsty, Mayerhanser, Katharina, Anbouba, Grace M., Armstrong-Javors, Amy, Bader, Ingrid, Baugh, Evan, Begtrup, Amber, Bupp, Caleb P., Callewaert, Bert L., Cereda, Anna, Cousin, Margot A., Del Rey Jimenez, Juan C., Demmer, Laurie, Dsouza, Nikita R., Fleischer, Nicole, Gavrilova, Ralitza H., Ghate, Sumedha, Graf, Elisabeth, Green, Andrew, Green, Sarah R., Iascone, Maria, Kdissa, Ameni, Klee, Dirk, Klee, Eric W., Lancaster, Emily, Lindstrom, Kristin, Mayr, Johannes A., McEntagart, Meriel, Meeks, Naomi J. L., Mittag, Dana, Moore, Harrison, Olsen, Anne K., Ortiz, Damara, Parsons, Gretchen, Pena, Loren D. M., Person, Richard E., Punj, Sumit, Ramos-Rivera, Gonzalo Alonso, Sacoto, Maria J. Guillen, Bradley Schaefer, G., Schnur, Rhonda E., Scott, Tiana M., Scott, Daryl A., Serbinski, Carolyn R., Shashi, Vandana, Siu, Victoria M., Stadheim, Barbro Fossøy, Sullivan, Jennifer A., Švantnerová, Jana, Velsher, Lea, Wargowski, David S., Wentzensen, Ingrid M., Wieczorek, Dagmar, Winkelmann, Juliane, Yap, Patrick, Zech, Michael, Zimmermann, Michael T., Meitinger, Thomas, Distelmaier, Felix, and Wagner, Matias
- Published
- 2021
- Full Text
- View/download PDF
46. NEXMIF encephalopathy: an X-linked disorder with male and female phenotypic patterns
- Author
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Stamberger, Hannah, Hammer, Trine B., Gardella, Elena, Vlaskamp, Danique R. M., Bertelsen, Birgitte, Mandelstam, Simone, de Lange, Iris, Zhang, Jing, Myers, Candace T., Fenger, Christina, Afawi, Zaid, Almanza Fuerte, Edith P., Andrade, Danielle M., Balcik, Yunus, Ben Zeev, Bruria, Bennett, Mark F., Berkovic, Samuel F., Isidor, Bertrand, Bouman, Arjan, Brilstra, Eva, Busk, Øyvind L., Cairns, Anita, Caumes, Roseline, Chatron, Nicolas, Dale, Russell C., de Geus, Christa, Edery, Patrick, Gill, Deepak, Granild-Jensen, Jacob Bie, Gunderson, Lauren, Gunning, Boudewijn, Heimer, Gali, Helle, Johan R., Hildebrand, Michael S., Hollingsworth, Georgie, Kharytonov, Volodymyr, Klee, Eric W., Koeleman, Bobby P. C., Koolen, David A., Korff, Christian, Küry, Sébastien, Lesca, Gaetan, Lev, Dorit, Leventer, Richard J., Mackay, Mark T., Macke, Erica L., McEntagart, Meriel, Mohammad, Shekeeb S., Monin, Pauline, Montomoli, Martino, Morava, Eva, Moutton, Sebastien, Muir, Alison M., Parrini, Elena, Procopis, Peter, Ranza, Emmanuelle, Reed, Laura, Reif, Philipp S., Rosenow, Felix, Rossi, Massimiliano, Sadleir, Lynette G., Sadoway, Tara, Schelhaas, Helenius J., Schneider, Amy L., Shah, Krati, Shalev, Ruth, Sisodiya, Sanjay M., Smol, Thomas, Stumpel, Connie T. R. M., Stuurman, Kyra, Symonds, Joseph D., Mau-Them, Frederic Tran, Verbeek, Nienke, Verhoeven, Judith S., Wallace, Geoffrey, Yosovich, Keren, Zarate, Yuri A., Zerem, Ayelet, Zuberi, Sameer M., Guerrini, Renzo, Mefford, Heather C., Patel, Chirag, Zhang, Yue-Hua, Møller, Rikke S., and Scheffer, Ingrid E.
- Published
- 2021
- Full Text
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47. Enhancing Patient Care in Rare Genetic Diseases: An HPO-based Phenotyping Pipeline
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Xiao, Yao, primary, Enayati, Moein, additional, Schaeferle, Gavin M., additional, Lanpher, Brendan C., additional, Klee, Eric W., additional, and Ngufor, Che, additional
- Published
- 2023
- Full Text
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48. HELLO: improved neural network architectures and methodologies for small variant calling
- Author
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Ramachandran, Anand, Lumetta, Steven S., Klee, Eric W., and Chen, Deming
- Published
- 2021
- Full Text
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49. Design considerations for workflow management systems use in production genomics research and the clinic
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Ahmed, Azza E., Allen, Joshua M., Bhat, Tajesvi, Burra, Prakruthi, Fliege, Christina E., Hart, Steven N., Heldenbrand, Jacob R., Hudson, Matthew E., Istanto, Dave Deandre, Kalmbach, Michael T., Kapraun, Gregory D., Kendig, Katherine I., Kendzior, Matthew Charles, Klee, Eric W., Mattson, Nate, Ross, Christian A., Sharif, Sami M., Venkatakrishnan, Ramshankar, Fadlelmola, Faisal M., and Mainzer, Liudmila S.
- Published
- 2021
- Full Text
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50. Epigenetic alteration contributes to the transcriptional reprogramming in T-cell prolymphocytic leukemia
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Tian, Shulan, Zhang, Henan, Zhang, Pan, Kalmbach, Michael, Lee, Jeong-Heon, Ordog, Tamas, Hampel, Paul J., Call, Timothy G., Witzig, Thomas E., Kay, Neil E., Klee, Eric W., Slager, Susan L., Yan, Huihuang, and Ding, Wei
- Published
- 2021
- Full Text
- View/download PDF
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