56 results on '"Towne, Meghan C"'
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52. An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge
- Author
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Brownstein, Catherine A, primary, Beggs, Alan H, additional, Homer, Nils, additional, Merriman, Barry, additional, Yu, Timothy W, additional, Flannery, Katherine C, additional, DeChene, Elizabeth T, additional, Towne, Meghan C, additional, Savage, Sarah K, additional, Price, Emily N, additional, Holm, Ingrid A, additional, Luquette, Lovelace J, additional, Lyon, Elaine, additional, Majzoub, Joseph, additional, Neupert, Peter, additional, McCallie Jr, David, additional, Szolovits, Peter, additional, Willard, Huntington F, additional, Mendelsohn, Nancy J, additional, Temme, Renee, additional, Finkel, Richard S, additional, Yum, Sabrina W, additional, Medne, Livija, additional, Sunyaev, Shamil R, additional, Adzhubey, Ivan, additional, Cassa, Christopher A, additional, de Bakker, Paul IW, additional, Duzkale, Hatice, additional, Dworzyński, Piotr, additional, Fairbrother, William, additional, Francioli, Laurent, additional, Funke, Birgit H, additional, Giovanni, Monica A, additional, Handsaker, Robert E, additional, Lage, Kasper, additional, Lebo, Matthew S, additional, Lek, Monkol, additional, Leshchiner, Ignaty, additional, MacArthur, Daniel G, additional, McLaughlin, Heather M, additional, Murray, Michael F, additional, Pers, Tune H, additional, Polak, Paz P, additional, Raychaudhuri, Soumya, additional, Rehm, Heidi L, additional, Soemedi, Rachel, additional, Stitziel, Nathan O, additional, Vestecka, Sara, additional, Supper, Jochen, additional, Gugenmus, Claudia, additional, Klocke, Bernward, additional, Hahn, Alexander, additional, Schubach, Max, additional, Menzel, Mortiz, additional, Biskup, Saskia, additional, Freisinger, Peter, additional, Deng, Mario, additional, Braun, Martin, additional, Perner, Sven, additional, Smith, Richard JH, additional, Andorf, Janeen L, additional, Huang, Jian, additional, Ryckman, Kelli, additional, Sheffield, Val C, additional, Stone, Edwin M, additional, Bair, Thomas, additional, Black-Ziegelbein, E, additional, Braun, Terry A, additional, Darbro, Benjamin, additional, DeLuca, Adam P, additional, Kolbe, Diana L, additional, Scheetz, Todd E, additional, Shearer, Aiden E, additional, Sompallae, Rama, additional, Wang, Kai, additional, Bassuk, Alexander G, additional, Edens, Erik, additional, Mathews, Katherine, additional, Moore, Steven A, additional, Shchelochkov, Oleg A, additional, Trapane, Pamela, additional, Bossler, Aaron, additional, Campbell, Colleen A, additional, Heusel, Jonathan W, additional, Kwitek, Anne, additional, Maga, Tara, additional, Panzer, Karin, additional, Wassink, Thomas, additional, Van Daele, Douglas, additional, Azaiez, Hela, additional, Booth, Kevin, additional, Meyer, Nic, additional, Segal, Michael M, additional, Williams, Marc S, additional, Tromp, Gerard, additional, White, Peter, additional, Corsmeier, Donald, additional, Fitzgerald-Butt, Sara, additional, Herman, Gail, additional, Lamb-Thrush, Devon, additional, McBride, Kim L, additional, Newsom, David, additional, Pierson, Christopher R, additional, Rakowsky, Alexander T, additional, Maver, Aleš, additional, Lovrečić, Luca, additional, Palandačić, Anja, additional, Peterlin, Borut, additional, Torkamani, Ali, additional, Wedell, Anna, additional, Huss, Mikael, additional, Alexeyenko, Andrey, additional, Lindvall, Jessica M, additional, Magnusson, Måns, additional, Nilsson, Daniel, additional, Stranneheim, Henrik, additional, Taylan, Fulya, additional, Gilissen, Christian, additional, Hoischen, Alexander, additional, van Bon, Bregje, additional, Yntema, Helger, additional, Nelen, Marcel, additional, Zhang, Weidong, additional, Sager, Jason, additional, Zhang, Lu, additional, Blair, Kathryn, additional, Kural, Deniz, additional, Cariaso, Michael, additional, Lennon, Greg G, additional, Javed, Asif, additional, Agrawal, Saloni, additional, Ng, Pauline C, additional, Sandhu, Komal S, additional, Krishna, Shuba, additional, Veeramachaneni, Vamsi, additional, Isakov, Ofer, additional, Halperin, Eran, additional, Friedman, Eitan, additional, Shomron, Noam, additional, Glusman, Gustavo, additional, Roach, Jared C, additional, Caballero, Juan, additional, Cox, Hannah C, additional, Mauldin, Denise, additional, Ament, Seth A, additional, Rowen, Lee, additional, Richards, Daniel R, additional, Lucas, F Anthony, additional, Gonzalez-Garay, Manuel L, additional, Caskey, C, additional, Bai, Yu, additional, Huang, Ying, additional, Fang, Fang, additional, Zhang, Yan, additional, Wang, Zhengyuan, additional, Barrera, Jorge, additional, Garcia-Lobo, Juan M, additional, González-Lamuño, Domingo, additional, Llorca, Javier, additional, Rodriguez, Maria C, additional, Varela, Ignacio, additional, Reese, Martin G, additional, De La Vega, Francisco M, additional, Kiruluta, Edward, additional, Cargill, Michele, additional, Hart, Reece K, additional, Sorenson, Jon M, additional, Lyon, Gholson J, additional, Stevenson, David A, additional, Bray, Bruce E, additional, Moore, Barry M, additional, Eilbeck, Karen, additional, Yandell, Mark, additional, Zhao, Hongyu, additional, Hou, Lin, additional, Chen, Xiaowei, additional, Yan, Xiting, additional, Chen, Mengjie, additional, Li, Cong, additional, Yang, Can, additional, Gunel, Murat, additional, Li, Peining, additional, Kong, Yong, additional, Alexander, Austin C, additional, Albertyn, Zayed I, additional, Boycott, Kym M, additional, Bulman, Dennis E, additional, Gordon, Paul MK, additional, Innes, A, additional, Knoppers, Bartha M, additional, Majewski, Jacek, additional, Marshall, Christian R, additional, Parboosingh, Jillian S, additional, Sawyer, Sarah L, additional, Samuels, Mark E, additional, Schwartzentruber, Jeremy, additional, Kohane, Isaac S, additional, and Margulies, David M, additional
- Published
- 2014
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53. Whole Exome Sequencing Identifies RAI1Mutation in a Morbidly Obese Child Diagnosed With ROHHAD Syndrome
- Author
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Thaker, Vidhu V., Esteves, Kristyn M., Towne, Meghan C., Brownstein, Catherine A., James, Philip M., Crowley, Laura, Hirschhorn, Joel N., Elsea, Sarah H., Beggs, Alan H., Picker, Jonathan, and Agrawal, Pankaj B.
- Abstract
Context:The current obesity epidemic is attributed to complex interactions between genetic and environmental factors. However, a limited number of cases, especially those with early-onset severe obesity, are linked to single gene defects. Rapid-onset obesity with hypothalamic dysfunction, hypoventilation and autonomic dysregulation (ROHHAD) is one of the syndromes that presents with abrupt-onset extreme weight gain with an unknown genetic basis.Objective:To identify the underlying genetic etiology in a child with morbid early-onset obesity, hypoventilation, and autonomic and behavioral disturbances who was clinically diagnosed with ROHHAD syndrome.Design/Setting/Intervention:The index patient was evaluated at an academic medical center. Whole-exome sequencing was performed on the proband and his parents. Genetic variants were validated by Sanger sequencing.Results:We identified a novel de novo nonsense mutation, c.3265 C>T (p.R1089X), in the retinoic acid-induced 1 (RAI1) gene in the proband. Mutations in the RAI1gene are known to cause Smith-Magenis syndrome (SMS). On further evaluation, his clinical features were not typical of either SMS or ROHHAD syndrome.Conclusions:This study identifies a de novo RAI1mutation in a child with morbid obesity and a clinical diagnosis of ROHHAD syndrome. Although extreme early-onset obesity, autonomic disturbances, and hypoventilation are present in ROHHAD, several of the clinical findings are consistent with SMS. This case highlights the challenges in the diagnosis of ROHHAD syndrome and its potential overlap with SMS. We also propose RAI1as a candidate gene for children with morbid obesity.
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- 2015
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54. Exome sequencing results in successful diagnosis and treatment of a severe congenital anemia
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Lacy, Jessica N., Ulirsch, Jacob C., Grace, Rachael F., Towne, Meghan C., Hale, John, Mohandas, Narla, Lux, Samuel E., Agrawal, Pankaj B., and Sankaran, Vijay G.
- Subjects
chronic hemolytic anemia ,congenital hemolytic anemia - Abstract
Whole-exome sequencing is increasingly used for diagnosis and identification of appropriate therapies in patients. Here, we present the case of a 3-yr-old male with a lifelong and severe transfusion-dependent anemia of unclear etiology, despite an extensive clinical workup. Given the difficulty of making the diagnosis and the potential side effects from performing interventions in patients with a congenital anemia of unknown etiology, we opted to perform whole-exome sequencing on the patient and his parents. This resulted in the identification of homozygous loss-of-function mutations in the EPB41 gene, encoding erythrocyte protein band 4.1, which therefore causes a rare and severe form of hereditary elliptocytosis in the patient. Based on prior clinical experience in similar patients, a surgical splenectomy was performed that resulted in subsequent transfusion independence in the patient. This case illustrates how whole-exome sequencing can lead to accurate diagnoses (and exclusion of diagnoses where interventions, such as splenectomy, would be contraindicated), thereby resulting in appropriate and successful therapeutic intervention—a major goal of precision medicine.
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- 2016
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55. A novel de novo mutation in ATP1A3 and childhood-onset schizophrenia
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Smedemark-Margulies, Niklas, Brownstein, Catherine A., Vargas, Sigella, Tembulkar, Sahil K., Towne, Meghan C., Shi, Jiahai, Gonzalez-Cuevas, Elisa, Liu, Kevin X., Bilguvar, Kaya, Kleiman, Robin J., Han, Min-Joon, Torres, Alcy, Berry, Gerard T., Yu, Timothy W., Beggs, Alan H., Agrawal, Pankaj B., and Gonzalez-Heydrich, Joseph
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psychotic mentation - Abstract
We describe a child with onset of command auditory hallucinations and behavioral regression at 6 yr of age in the context of longer standing selective mutism, aggression, and mild motor delays. His genetic evaluation included chromosomal microarray analysis and whole-exome sequencing. Sequencing revealed a previously unreported heterozygous de novo mutation c.385G>A in ATP1A3, predicted to result in a p.V129M amino acid change. This gene codes for a neuron-specific isoform of the catalytic α-subunit of the ATP-dependent transmembrane sodium–potassium pump. Heterozygous mutations in this gene have been reported as causing both sporadic and inherited forms of alternating hemiplegia of childhood and rapid-onset dystonia parkinsonism. We discuss the literature on phenotypes associated with known variants in ATP1A3, examine past functional studies of the role of ATP1A3 in neuronal function, and describe a novel clinical presentation associated with mutation of this gene.
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- 2016
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56. RNA methyltransferase SPOUT1/CENP-32 links mitotic spindle organization with the neurodevelopmental disorder SpADMiSS.
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Dharmadhikari AV, Abad MA, Khan S, Maroofian R, Sands TT, Ullah F, Samejima I, Wear MA, Moore KE, Kondakova E, Mitina N, Schaub T, Lee GK, Umandap CH, Berger SM, Iglesias AD, Popp B, Jamra RA, Gabriel H, Rentas S, Rippert AL, Izumi K, Conlin LK, Koboldt DC, Mosher TM, Hickey SE, Albert DVF, Norwood H, Lewanda AF, Dai H, Liu P, Mitani T, Marafi D, Pehlivan D, Posey JE, Lippa N, Vena N, Heinzen EL, Goldstein DB, Mignot C, de Sainte Agathe JM, Al-Sannaa NA, Zamani M, Sadeghian S, Azizimalamiri R, Seifia T, Zaki MS, Abdel-Salam GMH, Abdel-Hamid M, Alabdi L, Alkuraya FS, Dawoud H, Lofty A, Bauer P, Zifarelli G, Afzal E, Zafar F, Efthymiou S, Gossett D, Towne MC, Yeneabat R, Wontakal SN, Aggarwal VS, Rosenfeld JA, Tarabykin V, Ohta S, Lupski JR, Houlden H, Earnshaw WC, Davis EE, Jeyaprakash AA, and Liao J
- Abstract
SPOUT1/CENP-32 encodes a putative SPOUT RNA methyltransferase previously identified as a mitotic chromosome associated protein. SPOUT1/CENP-32 depletion leads to centrosome detachment from the spindle poles and chromosome misalignment. Aided by gene matching platforms, we identified 24 individuals with neurodevelopmental delays from 18 families with bi-allelic variants in SPOUT1/CENP-32 detected by exome/genome sequencing. Zebrafish spout1/cenp-32 mutants showed reduction in larval head size with concomitant apoptosis likely associated with altered cell cycle progression. In vivo complementation assays in zebrafish indicated that SPOUT1/CENP-32 missense variants identified in humans are pathogenic. Crystal structure analysis of SPOUT1/CENP-32 revealed that most disease-associated missense variants mapped to the catalytic domain. Additionally, SPOUT1/CENP-32 recurrent missense variants had reduced methyltransferase activity in vitro and compromised centrosome tethering to the spindle poles in human cells. Thus, SPOUT1/CENP-32 pathogenic variants cause an autosomal recessive neurodevelopmental disorder: SpADMiSS ( SPOUT1 Associated Development delay Microcephaly Seizures Short stature) underpinned by mitotic spindle organization defects and consequent chromosome segregation errors.
- Published
- 2024
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