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1. MSL2 variants lead to a neurodevelopmental syndrome with lack of coordination, epilepsy, specific dysmorphisms, and a distinct episignature.

Author

Karayol, Remzi, Borroto, Maria, Haghshenas, Sadegheh, Namasivayam, Anoja, Reilly, Jack, Levy, Michael, Relator, Raissa, Kerkhof, Jennifer, McConkey, Haley, Shvedunova, Maria, Petersen, Andrea, Magnussen, Kari, Zweier, Christiane, Vasileiou, Georgia, Reis, André, Savatt, Juliann, Mulligan, Meghan, Bicknell, Louise, Poke, Gemma, Abu-El-Haija, Aya, Duis, Jessica, Hannig, Vickie, Srivastava, Siddharth, Barkoudah, Elizabeth, Hauser, Natalie, van den Born, Myrthe, Hamiel, Uri, Henig, Noa, Baris Feldman, Hagit, McKee, Shane, Krapels, Ingrid, Lei, Yunping, Todorova, Albena, Yordanova, Ralitsa, Atemin, Slavena, Rogac, Mihael, McConnell, Vivienne, Chassevent, Anna, Barañano, Kristin, Shashi, Vandana, Sullivan, Jennifer, Peron, Angela, Iascone, Maria, Canevini, Maria, Friedman, Jennifer, Reyes, Iris, Kierstein, Janell, Shen, Joseph, Ahmed, Faria, Mao, Xiao, Almoguera, Berta, Blanco-Kelly, Fiona, Platzer, Konrad, Treu, Ariana-Berenike, Quilichini, Juliette, Bourgois, Alexia, Chatron, Nicolas, Januel, Louis, Rougeot, Christelle, Carere, Deanna, Monaghan, Kristin, Rousseau, Justine, Myers, Kenneth, Sadikovic, Bekim, Akhtar, Asifa, and Campeau, Philippe

Subjects
MSL2, autism, connective tissue, epigenetics, epilepsy, episignature, iPSC, male-specific lethal complex, neurodevelopmental syndrome, Adolescent, Child, Child, Preschool, Female, Humans, Male, Developmental Disabilities, DNA Methylation, Epigenesis, Genetic, Epilepsy, Histones, Induced Pluripotent Stem Cells, Intellectual Disability, Neurodevelopmental Disorders, Phenotype, Ubiquitin-Protein Ligases
Abstract

Epigenetic dysregulation has emerged as an important etiological mechanism of neurodevelopmental disorders (NDDs). Pathogenic variation in epigenetic regulators can impair deposition of histone post-translational modifications leading to aberrant spatiotemporal gene expression during neurodevelopment. The male-specific lethal (MSL) complex is a prominent multi-subunit epigenetic regulator of gene expression and is responsible for histone 4 lysine 16 acetylation (H4K16ac). Using exome sequencing, here we identify a cohort of 25 individuals with heterozygous de novo variants in MSL complex member MSL2. MSL2 variants were associated with NDD phenotypes including global developmental delay, intellectual disability, hypotonia, and motor issues such as coordination problems, feeding difficulties, and gait disturbance. Dysmorphisms and behavioral and/or psychiatric conditions, including autism spectrum disorder, and to a lesser extent, seizures, connective tissue disease signs, sleep disturbance, vision problems, and other organ anomalies, were observed in affected individuals. As a molecular biomarker, a sensitive and specific DNA methylation episignature has been established. Induced pluripotent stem cells (iPSCs) derived from three members of our cohort exhibited reduced MSL2 levels. Remarkably, while NDD-associated variants in two other members of the MSL complex (MOF and MSL3) result in reduced H4K16ac, global H4K16ac levels are unchanged in iPSCs with MSL2 variants. Regardless, MSL2 variants altered the expression of MSL2 targets in iPSCs and upon their differentiation to early germ layers. Our study defines an MSL2-related disorder as an NDD with distinguishable clinical features, a specific blood DNA episignature, and a distinct, MSL2-specific molecular etiology compared to other MSL complex-related disorders.

Published
2024

2. De Novo Variants in RAB11B Cause Various Degrees of Global Developmental Delay and Intellectual Disability in Children

Author

Ahmad, Natalie, Fazeli, Walid, Schließke, Sophia, Lesca, Gaetan, Gokce-Samar, Zeynep, Mekbib, Kedous Y., Jin, Sheng Chih, Burton, Jennifer, Hoganson, George, Petersen, Andrea, Gracie, Sara, Granger, Leslie, Bartels, Enrika, Oppermann, Henry, Kundishora, Adam, Till, Marianne, Milleret-Pignot, Clara, Dangerfield, Shane, Viskochil, David, Anderson, Katherine J., Palculict, Timothy Blake, Schnur, Rhonda E., Wentzensen, Ingrid M., Tiller, George E., Kahle, Kristopher T., Kunz, Wolfram S., Burkart, Sebastian, Simons, Matias, Sticht, Heinrich, Abou Jamra, Rami, and Neuser, Sonja

Published
2023
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3. Mutation-specific pathophysiological mechanisms define different neurodevelopmental disorders associated with SATB1 dysfunction.

Author

den Hoed, Joery, de Boer, Elke, Voisin, Norine, Dingemans, Alexander, Guex, Nicolas, Wiel, Laurens, Nellaker, Christoffer, Amudhavalli, Shivarajan, Banka, Siddharth, Bena, Frederique, Ben-Zeev, Bruria, Bonagura, Vincent, Bruel, Ange-Line, Brunet, Theresa, Brunner, Han, Chew, Hui, Chrast, Jacqueline, Cimbalistienė, Loreta, Coon, Hilary, Délot, Emmanuèlle, Démurger, Florence, Denommé-Pichon, Anne-Sophie, Depienne, Christel, Donnai, Dian, Dyment, David, Elpeleg, Orly, Faivre, Laurence, Gilissen, Christian, Granger, Leslie, Haber, Benjamin, Hachiya, Yasuo, Abedi, Yasmin, Hanebeck, Jennifer, Hehir-Kwa, Jayne, Horist, Brooke, Itai, Toshiyuki, Jackson, Adam, Jewell, Rosalyn, Jones, Kelly, Joss, Shelagh, Kashii, Hirofumi, Kato, Mitsuhiro, Kattentidt-Mouravieva, Anja, Kok, Fernando, Kotzaeridou, Urania, Krishnamurthy, Vidya, Kučinskas, Vaidutis, Kuechler, Alma, Lavillaureix, Alinoë, Liu, Pengfei, Manwaring, Linda, Matsumoto, Naomichi, Mazel, Benoît, McWalter, Kirsty, Meiner, Vardiella, Mikati, Mohamad, Miyatake, Satoko, Mizuguchi, Takeshi, Moey, Lip, Mohammed, Shehla, Mor-Shaked, Hagar, Mountford, Hayley, Newbury-Ecob, Ruth, Odent, Sylvie, Orec, Laura, Osmond, Matthew, Palculict, Timothy, Parker, Michael, Petersen, Andrea, Pfundt, Rolph, Preikšaitienė, Eglė, Radtke, Kelly, Ranza, Emmanuelle, Rosenfeld, Jill, Santiago-Sim, Teresa, Schwager, Caitlin, Sinnema, Margje, Snijders Blok, Lot, Spillmann, Rebecca, Stegmann, Alexander, Thiffault, Isabelle, Tran, Linh, Vaknin-Dembinsky, Adi, Vedovato-Dos-Santos, Juliana, Schrier Vergano, Samantha, Vilain, Eric, Vitobello, Antonio, Wagner, Matias, Waheeb, Androu, Willing, Marcia, Zuccarelli, Britton, Kini, Usha, Newbury, Dianne, Kleefstra, Tjitske, Reymond, Alexandre, Fisher, Simon, and Vissers, Lisenka

Subjects
HPO-based analysis, SATB1, cell-based functional assays, de novo variants, intellectual disability, neurodevelopmental disorders, seizures, teeth abnormalities, Chromatin, Female, Genetic Association Studies, Haploinsufficiency, Humans, Male, Matrix Attachment Region Binding Proteins, Models, Molecular, Mutation, Mutation, Missense, Neurodevelopmental Disorders, Protein Binding, Protein Domains, Transcription, Genetic
Abstract

Whereas large-scale statistical analyses can robustly identify disease-gene relationships, they do not accurately capture genotype-phenotype correlations or disease mechanisms. We use multiple lines of independent evidence to show that different variant types in a single gene, SATB1, cause clinically overlapping but distinct neurodevelopmental disorders. Clinical evaluation of 42 individuals carrying SATB1 variants identified overt genotype-phenotype relationships, associated with different pathophysiological mechanisms, established by functional assays. Missense variants in the CUT1 and CUT2 DNA-binding domains result in stronger chromatin binding, increased transcriptional repression, and a severe phenotype. In contrast, variants predicted to result in haploinsufficiency are associated with a milder clinical presentation. A similarly mild phenotype is observed for individuals with premature protein truncating variants that escape nonsense-mediated decay, which are transcriptionally active but mislocalized in the cell. Our results suggest that in-depth mutation-specific genotype-phenotype studies are essential to capture full disease complexity and to explain phenotypic variability.

Published
2021

4. ADGRL1 haploinsufficiency causes a variable spectrum of neurodevelopmental disorders in humans and alters synaptic activity and behavior in a mouse model

Author

Vitobello, Antonio, Mazel, Benoit, Lelianova, Vera G., Zangrandi, Alice, Petitto, Evelina, Suckling, Jason, Salpietro, Vincenzo, Meyer, Robert, Elbracht, Miriam, Kurth, Ingo, Eggermann, Thomas, Benlaouer, Ouafa, Lall, Gurprit, Tonevitsky, Alexander G., Scott, Daryl A., Chan, Katie M., Rosenfeld, Jill A., Nambot, Sophie, Safraou, Hana, Bruel, Ange-Line, Denommé-Pichon, Anne-Sophie, Tran Mau-Them, Frédéric, Philippe, Christophe, Duffourd, Yannis, Guo, Hui, Petersen, Andrea K., Granger, Leslie, Crunk, Amy, Bayat, Allan, Striano, Pasquale, Zara, Federico, Scala, Marcello, Thomas, Quentin, Delahaye, Andrée, de Sainte Agathe, Jean-Madeleine, Buratti, Julien, Kozlov, Serguei V., Faivre, Laurence, Thauvin-Robinet, Christel, and Ushkaryov, Yuri

Published
2022
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5. Spliceosome malfunction causes neurodevelopmental disorders with overlapping features

Author

Genetica, Genetica Sectie Research, Cancer, Child Health, Li, Dong, Wang, Qin, Bayat, Allan, Battig, Mark R., Zhou, Yijing, Bosch, Daniëlle G.M., van Haaften, Gijs, Granger, Leslie, Petersen, Andrea K., Pérez-Jurado, Luis A., Aznar-Laín, Gemma, Aneja, Anushree, Hancarova, Miroslava, Bendova, Sarka, Schwarz, Martin, Pourova, Radka Kremlikova, Sedlacek, Zdenek, Keena, Beth A., March, Michael E., Hou, Cuiping, O’Connor, Nora, Bhoj, Elizabeth J., Harr, Margaret H., Lemire, Gabrielle, Boycott, Kym M., Towne, Meghan, Li, Megan, Tarnopolsky, Mark, Brady, Lauren, Parker, Michael J., Faghfoury, Hanna, Parsley, Lea Kristin, Agolini, Emanuele, Dentici, Maria Lisa, Novelli, Antonio, Wright, Meredith, Palmquist, Rachel, Lai, Khanh, Scala, Marcello, Striano, Pasquale, Iacomino, Michele, Zara, Federico, Cooper, Annina, Maarup, Timothy J., Byler, Melissa, Lebel, Robert Roger, Balci, Tugce B., Louie, Raymond, Lyons, Michael, Douglas, Jessica, Nowak, Catherine, Afenjar, Alexandra, Hoyer, Juliane, Keren, Boris, Maas, Saskia M., Motazacker, Mahdi M., Martinez-Agosto, Julian A., Rabani, Ahna M., McCormick, Elizabeth M., Falk, Marni J., Ruggiero, Sarah M., Helbig, Ingo, Møller, Rikke S., Tessarollo, Lino, Ardori, Francesco Tomassoni, Palko, Mary Ellen, Hsieh, Tzung Chien, Krawitz, Peter M., Ganapathi, Mythily, Gelb, Bruce D., Jobanputra, Vaidehi, Wilson, Ashley, Greally, John, Jacquemont, Sébastien, Jizi, Khadijé, Bruel, Ange Line, Quelin, Chloé, Misra, Vinod K., Chick, Erika, Romano, Corrado, Greco, Donatella, Arena, Alessia, Morleo, Manuela, Nigro, Vincenzo, Seyama, Rie, Uchiyama, Yuri, Matsumoto, Naomichi, Taira, Ryoji, Tashiro, Katsuya, Sakai, Yasunari, Yigit, Gökhan, Wollnik, Bernd, Wagner, Michael, Kutsche, Barbara, Hurst, Anna C.E., Thompson, Michelle L., Schmidt, Ryan, Randolph, Linda, Spillmann, Rebecca C., Shashi, Vandana, Higginbotham, Edward J., Cordeiro, Dawn, Carnevale, Amanda, Costain, Gregory, Khan, Tayyaba, Funalot, Benoît, Mau-Them, Frederic Tran, Garcia Moya, Luis Fernandez, García-Miñaúr, Sixto, Osmond, Matthew, Chad, Lauren, Quercia, Nada, Carrasco, Diana, Li, Chumei, Sanchez-Valle, Amarilis, Kelley, Meghan, Nizon, Mathilde, Jensson, Brynjar O., Sulem, Patrick, Stefansson, Kari, Gorokhova, Svetlana, Busa, Tiffany, Rio, Marlène, Habdallah, Hamza Hadj, Lesieur-Sebellin, Marion, Amiel, Jeanne, Pingault, Véronique, Mercier, Sandra, Vincent, Marie, Philippe, Christophe, Fatus-Fauconnier, Clemence, Friend, Kathryn, Halligan, Rebecca K., Biswas, Sunita, Rosser, Jane, Shoubridge, Cheryl, Corbett, Mark, Barnett, Christopher, Gecz, Jozef, Leppig, Kathleen, Slavotinek, Anne, Marcelis, Carlo, Pfundt, Rolph, de Vries, Bert B.A., van Slegtenhorst, Marjon A., Brooks, Alice S., Cogne, Benjamin, Rambaud, Thomas, Tümer, Zeynep, Zackai, Elaine H., Akizu, Naiara, Song, Yuanquan, Hakonarson, Hakon, Genetica, Genetica Sectie Research, Cancer, Child Health, Li, Dong, Wang, Qin, Bayat, Allan, Battig, Mark R., Zhou, Yijing, Bosch, Daniëlle G.M., van Haaften, Gijs, Granger, Leslie, Petersen, Andrea K., Pérez-Jurado, Luis A., Aznar-Laín, Gemma, Aneja, Anushree, Hancarova, Miroslava, Bendova, Sarka, Schwarz, Martin, Pourova, Radka Kremlikova, Sedlacek, Zdenek, Keena, Beth A., March, Michael E., Hou, Cuiping, O’Connor, Nora, Bhoj, Elizabeth J., Harr, Margaret H., Lemire, Gabrielle, Boycott, Kym M., Towne, Meghan, Li, Megan, Tarnopolsky, Mark, Brady, Lauren, Parker, Michael J., Faghfoury, Hanna, Parsley, Lea Kristin, Agolini, Emanuele, Dentici, Maria Lisa, Novelli, Antonio, Wright, Meredith, Palmquist, Rachel, Lai, Khanh, Scala, Marcello, Striano, Pasquale, Iacomino, Michele, Zara, Federico, Cooper, Annina, Maarup, Timothy J., Byler, Melissa, Lebel, Robert Roger, Balci, Tugce B., Louie, Raymond, Lyons, Michael, Douglas, Jessica, Nowak, Catherine, Afenjar, Alexandra, Hoyer, Juliane, Keren, Boris, Maas, Saskia M., Motazacker, Mahdi M., Martinez-Agosto, Julian A., Rabani, Ahna M., McCormick, Elizabeth M., Falk, Marni J., Ruggiero, Sarah M., Helbig, Ingo, Møller, Rikke S., Tessarollo, Lino, Ardori, Francesco Tomassoni, Palko, Mary Ellen, Hsieh, Tzung Chien, Krawitz, Peter M., Ganapathi, Mythily, Gelb, Bruce D., Jobanputra, Vaidehi, Wilson, Ashley, Greally, John, Jacquemont, Sébastien, Jizi, Khadijé, Bruel, Ange Line, Quelin, Chloé, Misra, Vinod K., Chick, Erika, Romano, Corrado, Greco, Donatella, Arena, Alessia, Morleo, Manuela, Nigro, Vincenzo, Seyama, Rie, Uchiyama, Yuri, Matsumoto, Naomichi, Taira, Ryoji, Tashiro, Katsuya, Sakai, Yasunari, Yigit, Gökhan, Wollnik, Bernd, Wagner, Michael, Kutsche, Barbara, Hurst, Anna C.E., Thompson, Michelle L., Schmidt, Ryan, Randolph, Linda, Spillmann, Rebecca C., Shashi, Vandana, Higginbotham, Edward J., Cordeiro, Dawn, Carnevale, Amanda, Costain, Gregory, Khan, Tayyaba, Funalot, Benoît, Mau-Them, Frederic Tran, Garcia Moya, Luis Fernandez, García-Miñaúr, Sixto, Osmond, Matthew, Chad, Lauren, Quercia, Nada, Carrasco, Diana, Li, Chumei, Sanchez-Valle, Amarilis, Kelley, Meghan, Nizon, Mathilde, Jensson, Brynjar O., Sulem, Patrick, Stefansson, Kari, Gorokhova, Svetlana, Busa, Tiffany, Rio, Marlène, Habdallah, Hamza Hadj, Lesieur-Sebellin, Marion, Amiel, Jeanne, Pingault, Véronique, Mercier, Sandra, Vincent, Marie, Philippe, Christophe, Fatus-Fauconnier, Clemence, Friend, Kathryn, Halligan, Rebecca K., Biswas, Sunita, Rosser, Jane, Shoubridge, Cheryl, Corbett, Mark, Barnett, Christopher, Gecz, Jozef, Leppig, Kathleen, Slavotinek, Anne, Marcelis, Carlo, Pfundt, Rolph, de Vries, Bert B.A., van Slegtenhorst, Marjon A., Brooks, Alice S., Cogne, Benjamin, Rambaud, Thomas, Tümer, Zeynep, Zackai, Elaine H., Akizu, Naiara, Song, Yuanquan, and Hakonarson, Hakon

Published
2024

6. Spliceosome malfunction causes neurodevelopmental disorders with overlapping features

Author

Li, Dong, Wang, Qin, Bayat, Allan, Battig, Mark R., Zhou, Yijing, Bosch, Daniëlle G.M., van Haaften, Gijs, Granger, Leslie, Petersen, Andrea K., Pérez-Jurado, Luis A., Aznar-Laín, Gemma, Aneja, Anushree, Hancarova, Miroslava, Bendova, Sarka, Schwarz, Martin, Pourova, Radka Kremlikova, Sedlacek, Zdenek, Keena, Beth A., March, Michael E., Hou, Cuiping, O’Connor, Nora, Bhoj, Elizabeth J., Harr, Margaret H., Lemire, Gabrielle, Boycott, Kym M., Towne, Meghan, Li, Megan, Tarnopolsky, Mark, Brady, Lauren, Parker, Michael J., Faghfoury, Hanna, Parsley, Lea Kristin, Agolini, Emanuele, Dentici, Maria Lisa, Novelli, Antonio, Wright, Meredith, Palmquist, Rachel, Lai, Khanh, Scala, Marcello, Striano, Pasquale, Iacomino, Michele, Zara, Federico, Cooper, Annina, Maarup, Timothy J., Byler, Melissa, Lebel, Robert Roger, Balci, Tugce B., Louie, Raymond, Lyons, Michael, Douglas, Jessica, Nowak, Catherine, Afenjar, Alexandra, Hoyer, Juliane, Keren, Boris, Maas, Saskia M., Motazacker, Mahdi M., Martinez-Agosto, Julian A., Rabani, Ahna M., McCormick, Elizabeth M., Falk, Marni J., Ruggiero, Sarah M., Helbig, Ingo, Møller, Rikke S., Tessarollo, Lino, Ardori, Francesco Tomassoni, Palko, Mary Ellen, Hsieh, Tzung Chien, Krawitz, Peter M., Ganapathi, Mythily, Gelb, Bruce D., Jobanputra, Vaidehi, Wilson, Ashley, Greally, John, Jacquemont, Sébastien, Jizi, Khadijé, Bruel, Ange Line, Quelin, Chloé, Misra, Vinod K., Chick, Erika, Romano, Corrado, Greco, Donatella, Arena, Alessia, Morleo, Manuela, Nigro, Vincenzo, Seyama, Rie, Uchiyama, Yuri, Matsumoto, Naomichi, Taira, Ryoji, Tashiro, Katsuya, Sakai, Yasunari, Yigit, Gökhan, Wollnik, Bernd, Wagner, Michael, Kutsche, Barbara, Hurst, Anna C.E., Thompson, Michelle L., Schmidt, Ryan, Randolph, Linda, Spillmann, Rebecca C., Shashi, Vandana, Higginbotham, Edward J., Cordeiro, Dawn, Carnevale, Amanda, Costain, Gregory, Khan, Tayyaba, Funalot, Benoît, Mau-Them, Frederic Tran, Garcia Moya, Luis Fernandez, García-Miñaúr, Sixto, Osmond, Matthew, Chad, Lauren, Quercia, Nada, Carrasco, Diana, Li, Chumei, Sanchez-Valle, Amarilis, Kelley, Meghan, Nizon, Mathilde, Jensson, Brynjar O., Sulem, Patrick, Stefansson, Kari, Gorokhova, Svetlana, Busa, Tiffany, Rio, Marlène, Habdallah, Hamza Hadj, Lesieur-Sebellin, Marion, Amiel, Jeanne, Pingault, Véronique, Mercier, Sandra, Vincent, Marie, Philippe, Christophe, Fatus-Fauconnier, Clemence, Friend, Kathryn, Halligan, Rebecca K., Biswas, Sunita, Rosser, Jane, Shoubridge, Cheryl, Corbett, Mark, Barnett, Christopher, Gecz, Jozef, Leppig, Kathleen, Slavotinek, Anne, Marcelis, Carlo, Pfundt, Rolph, de Vries, Bert B.A., van Slegtenhorst, Marjon A., Brooks, Alice S., Cogne, Benjamin, Rambaud, Thomas, Tümer, Zeynep, Zackai, Elaine H., Akizu, Naiara, Song, Yuanquan, Hakonarson, Hakon, Li, Dong, Wang, Qin, Bayat, Allan, Battig, Mark R., Zhou, Yijing, Bosch, Daniëlle G.M., van Haaften, Gijs, Granger, Leslie, Petersen, Andrea K., Pérez-Jurado, Luis A., Aznar-Laín, Gemma, Aneja, Anushree, Hancarova, Miroslava, Bendova, Sarka, Schwarz, Martin, Pourova, Radka Kremlikova, Sedlacek, Zdenek, Keena, Beth A., March, Michael E., Hou, Cuiping, O’Connor, Nora, Bhoj, Elizabeth J., Harr, Margaret H., Lemire, Gabrielle, Boycott, Kym M., Towne, Meghan, Li, Megan, Tarnopolsky, Mark, Brady, Lauren, Parker, Michael J., Faghfoury, Hanna, Parsley, Lea Kristin, Agolini, Emanuele, Dentici, Maria Lisa, Novelli, Antonio, Wright, Meredith, Palmquist, Rachel, Lai, Khanh, Scala, Marcello, Striano, Pasquale, Iacomino, Michele, Zara, Federico, Cooper, Annina, Maarup, Timothy J., Byler, Melissa, Lebel, Robert Roger, Balci, Tugce B., Louie, Raymond, Lyons, Michael, Douglas, Jessica, Nowak, Catherine, Afenjar, Alexandra, Hoyer, Juliane, Keren, Boris, Maas, Saskia M., Motazacker, Mahdi M., Martinez-Agosto, Julian A., Rabani, Ahna M., McCormick, Elizabeth M., Falk, Marni J., Ruggiero, Sarah M., Helbig, Ingo, Møller, Rikke S., Tessarollo, Lino, Ardori, Francesco Tomassoni, Palko, Mary Ellen, Hsieh, Tzung Chien, Krawitz, Peter M., Ganapathi, Mythily, Gelb, Bruce D., Jobanputra, Vaidehi, Wilson, Ashley, Greally, John, Jacquemont, Sébastien, Jizi, Khadijé, Bruel, Ange Line, Quelin, Chloé, Misra, Vinod K., Chick, Erika, Romano, Corrado, Greco, Donatella, Arena, Alessia, Morleo, Manuela, Nigro, Vincenzo, Seyama, Rie, Uchiyama, Yuri, Matsumoto, Naomichi, Taira, Ryoji, Tashiro, Katsuya, Sakai, Yasunari, Yigit, Gökhan, Wollnik, Bernd, Wagner, Michael, Kutsche, Barbara, Hurst, Anna C.E., Thompson, Michelle L., Schmidt, Ryan, Randolph, Linda, Spillmann, Rebecca C., Shashi, Vandana, Higginbotham, Edward J., Cordeiro, Dawn, Carnevale, Amanda, Costain, Gregory, Khan, Tayyaba, Funalot, Benoît, Mau-Them, Frederic Tran, Garcia Moya, Luis Fernandez, García-Miñaúr, Sixto, Osmond, Matthew, Chad, Lauren, Quercia, Nada, Carrasco, Diana, Li, Chumei, Sanchez-Valle, Amarilis, Kelley, Meghan, Nizon, Mathilde, Jensson, Brynjar O., Sulem, Patrick, Stefansson, Kari, Gorokhova, Svetlana, Busa, Tiffany, Rio, Marlène, Habdallah, Hamza Hadj, Lesieur-Sebellin, Marion, Amiel, Jeanne, Pingault, Véronique, Mercier, Sandra, Vincent, Marie, Philippe, Christophe, Fatus-Fauconnier, Clemence, Friend, Kathryn, Halligan, Rebecca K., Biswas, Sunita, Rosser, Jane, Shoubridge, Cheryl, Corbett, Mark, Barnett, Christopher, Gecz, Jozef, Leppig, Kathleen, Slavotinek, Anne, Marcelis, Carlo, Pfundt, Rolph, de Vries, Bert B.A., van Slegtenhorst, Marjon A., Brooks, Alice S., Cogne, Benjamin, Rambaud, Thomas, Tümer, Zeynep, Zackai, Elaine H., Akizu, Naiara, Song, Yuanquan, and Hakonarson, Hakon

Abstract

Pre-mRNA splicing is a highly coordinated process. While its dysregulation has been linked to neurological deficits, our understanding of the underlying molecular and cellular mechanisms remains limited. We implicated pathogenic variants in U2AF2 and PRPF19, encoding spliceosome subunits in neurodevelopmental disorders (NDDs), by identifying 46 unrelated individuals with 23 de novo U2AF2 missense variants (including 7 recurrent variants in 30 individuals) and 6 individuals with de novo PRPF19 variants. Eight U2AF2 variants dysregulated splicing of a model substrate. Neuritogenesis was reduced in human neurons differentiated from human pluripotent stem cells carrying two U2AF2 hyper-recurrent variants. Neural loss of function (LoF) of the Drosophila orthologs U2af50 and Prp19 led to lethality, abnormal mushroom body (MB) patterning, and social deficits, which were differentially rescued by wild-type and mutant U2AF2 or PRPF19. Transcriptome profiling revealed splicing substrates or effectors (including Rbfox1, a third splicing factor), which rescued MB defects in U2af50deficient flies. Upon reanalysis of negative clinical exomes followed by data sharing, we further identified 6 patients with NDD who carried RBFOX1 missense variants which, by in vitro testing, showed LoF. Our study implicates 3 splicing factors as NDD-causative genes and establishes a genetic network with hierarchy underlying human brain development and function.

Published
2024

9. TINY MARVELS.

Author

Marcell, Allegra, Slack, Monica, Weidemoyer, Stephanie, Kurzik, George, Snider, Trisha, Martin, Olivia, Woods, Shawn, Harris, Scott, Petersen, Andrea, and Lynch-Pangie, Ronan

Published
2024

10. An empirical study of lawyers' capability to adapt to disruption in Queensland, Australia.

Author

Timoshanko, Aaron, Hart, Caroline, Bartlett, Francesca, Murray, Angus, and Perry-Petersen, Andrea

Subjects
COVID-19 pandemic, EMPIRICAL research, SMALL business, LAWYERS, INTERNET surveys, LAW firms
Abstract

An online survey of 261 Queensland legal practitioners working in sole, micro, small or medium-sized law firms provides valuable insights into their capability to successfully navigate disruption like that experienced during COVID-19. Our results indicated that respondent lawyers demonstrated progressiveness, openness and willingness to engage with innovative approaches, including technology, to build greater capacity within their firms. However, the results from the research identified several overlapping challenges faced by respondents that reduced their capability to adapt to disruption, including being time-poor and difficulty obtaining impartial and trustworthy information and training about emerging forms of disruption. [ABSTRACT FROM AUTHOR]

Published
2024
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11. Spliceosome malfunction causes neurodevelopmental disorders with overlapping features

Author

Li, Dong, primary, Wang, Qin, additional, Bayat, Allan, additional, Battig, Mark R., additional, Zhou, Yijing, additional, Bosch, Daniëlle G.M., additional, van Haaften, Gijs, additional, Granger, Leslie, additional, Petersen, Andrea K., additional, Pérez-Jurado, Luis A., additional, Aznar-Laín, Gemma, additional, Aneja, Anushree, additional, Hancarova, Miroslava, additional, Bendova, Sarka, additional, Schwarz, Martin, additional, Kremlíková Pourová, Radka, additional, Sedlacek, Zdenek, additional, Keena, Beth A., additional, March, Michael E., additional, Hou, Cuiping, additional, O'Connor, Nora, additional, Bhoj, Elizabeth J., additional, Harr, Margaret H., additional, Lemire, Gabrielle, additional, Boycott, Kym M., additional, Towne, Meghan C., additional, Li, Megan, additional, Tarnopolsky, Mark, additional, Brady, Lauren, additional, Parker, Michael J., additional, Faghfoury, Hanna, additional, Parsley, Lea Kristin, additional, Agolini, Emanuele, additional, Dentici, Maria Lisa, additional, Novelli, Antonio, additional, Wright, Meredith S., additional, Palmquist, Rachel, additional, Lai, Khanh, additional, Scala, Marcello, additional, Striano, Pasquale, additional, Iacomino, Michele, additional, Zara, Federico, additional, Cooper, Annina, additional, Maarup, Timothy J., additional, Byler, Melissa, additional, Lebel, Robert Roger, additional, Balci, Tugce B., additional, Louie, Raymond J., additional, Lyons, Michael J., additional, Douglas, Jessica, additional, Nowak, Catherine B., additional, Afenjar, Alexandra, additional, Hoyer, Juliane, additional, Keren, Boris, additional, Maas, Saskia M., additional, Motazacker, Mahdi M., additional, Martinez-Agosto, Julian A., additional, Rabani, Ahna M., additional, McCormick, Elizabeth M., additional, Falk, Marni, additional, Ruggiero, Sarah M., additional, Helbig, Ingo, additional, Møller, Rikke S., additional, Tessarollo, Lino, additional, Tomassoni-Ardori, Francesco, additional, Palko, Mary Ellen, additional, Hsieh, Tzung-Chien, additional, Krawitz, Peter M., additional, Ganapathi, Mythily, additional, Gelb, Bruce D., additional, Jobanputra, Vaidehi, additional, Wilson, Ashley, additional, Greally, John, additional, Jacquemont, Sébastien, additional, Jizi, Khadijé, additional, Ange-Line, Bruel, additional, Quelin, Chloé, additional, Misra, Vinod K., additional, Chick, Erika, additional, Romano, Corrado, additional, Greco, Donatella, additional, Arena, Alessia, additional, Morleo, Manuela, additional, Nigro, Vincenzo, additional, Seyama, Rie, additional, Uchiyama, Yuri, additional, Matsumoto, Naomichi, additional, Taira, Ryoji, additional, Tashiro, Katsuya, additional, Sakai, Yasunari, additional, Yigit, Gökhan, additional, Wollnik, Bernd, additional, Wagner, Michael, additional, Kutsche, Barbara, additional, Hurst, Anna C.E., additional, Thompson, Michelle L., additional, Schmidt, Ryan J., additional, Randolph, Linda M., additional, Spillmann, Rebecca C., additional, Shashi, Vandana, additional, Higginbotham, Edward J., additional, Cordeiro, Dawn, additional, Carnevale, Amanda, additional, Costain, Gregory, additional, Khan, Tayyaba, additional, Funalot, Benoît, additional, Tran Mau-Them, Frederic, additional, Fernandez Garcia Moya, Luis, additional, García-Miñaúr, Sixto, additional, Osmond, Matthew, additional, Chad, Lauren, additional, Quercia, Nada, additional, Carrasco, Diana, additional, Li, Chumei, additional, Sanchez-Valle, Amarilis, additional, Kelley, Meghan, additional, Nizon, Mathilde, additional, Jensson, Brynjar O., additional, Sulem, Patrick, additional, Stefansson, Kari, additional, Gorokhova, Svetlana, additional, Busa, Tiffany, additional, Rio, Marlène, additional, Hadj Abdallah, Hamza, additional, Lesieur-Sebellin, Marion, additional, Amiel, Jeanne, additional, Pingault, Véronique, additional, Mercier, Sandra, additional, Vincent, Marie, additional, Philippe, Christophe, additional, Fatus-Fauconnier, Clemence, additional, Friend, Kathryn, additional, Halligan, Rebecca K., additional, Biswas, Sunita, additional, Rosser, Jane M.R., additional, Shoubridge, Cheryl, additional, Corbett, Mark A., additional, Barnett, Christopher, additional, Gecz, Jozef, additional, Leppig, Kathleen A., additional, Slavotinek, Anne, additional, Marcelis, Carlo, additional, Pfundt, Rolph, additional, de Vries, Bert B.A., additional, van Slegtenhorst, Marjon A., additional, Brooks, Alice S., additional, Cogne, Benjamin, additional, Rambaud, Thomas, additional, Tümer, Zeynep, additional, Zackai, Elaine H., additional, Akizu, Naiara, additional, Song, Yuanquan, additional, and Hakonarson, Hakon, additional

Published
2023
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12. Perspectives of adolescents with neurofibromatosis 1 and cutaneous neurofibromas: Implications for clinical trials

Author

Cannon, Ashley, primary, Sarin, Kavita Y, additional, Petersen, Andrea K, additional, Pichard, Dominique C, additional, Wolters, Pamela L, additional, Erickson, Gregg, additional, Lessing, Andrés J, additional, Li, Peng, additional, Röhl, Claas, additional, Rosser, Tena, additional, Widemann, Brigitte C, additional, Blakeley, Jaishri O, additional, and Plotkin, Scott R, additional

Published
2023
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13. Perspectives of adolescents with neurofibromatosis 1 and cutaneous neurofibromas: Implications for clinical trials.

Author

Cannon, Ashley, Sarin, Kavita Y, Petersen, Andrea K, Pichard, Dominique C, Wolters, Pamela L, Erickson, Gregg, Lessing, Andrés J, Li, Peng, Röhl, Claas, Rosser, Tena, Widemann, Brigitte C, Blakeley, Jaishri O, and Plotkin, Scott R

Subjects
CAREGIVER attitudes, SELF-evaluation, DISEASES, NEUROFIBROMA, SKIN tumors, PATIENTS' attitudes, RISK assessment, SURVEYS, COMMUNICATION, RESEARCH funding, NEUROFIBROMATOSIS 1, EMOTIONS, ADOLESCENCE
Abstract

Background/Aims: More than 99% of individuals with neurofibromatosis 1 develop cutaneous neurofibromas, benign nerve sheath tumors that manifest as nodules on the skin. These cutaneous neurofibromas emerge with age, appearing most commonly in adolescence. Nevertheless, few data have been published on how adolescents with neurofibromatosis 1 feel about cutaneous neurofibromas. The purpose of this study was to assess the perspectives of adolescents with neurofibromatosis 1 and their caregivers regarding cutaneous neurofibroma morbidity, treatment options, and acceptable risks-benefits of treatment. Methods: An online survey was distributed through the world's largest NF registry. Eligibility criteria included self-reported neurofibromatosis 1 diagnosis, adolescent child ages 12–17 years, ≥1 cutaneous neurofibroma, and ability to read English. The survey was designed to collect details about the adolescent's cutaneous neurofibromas, views on morbidity related to cutaneous neurofibromas, social and emotional impact of cutaneous neurofibromas, communication regarding cutaneous neurofibromas, and views regarding current and potential future cutaneous neurofibroma treatment. Results: Survey respondents included 28 adolescents and 32 caregivers. Adolescents reported having several negative feelings about cutaneous neurofibromas, particularly feeling worried about the potential progression of their cutaneous neurofibromas (50%). Pruritus (34%), location (34%), appearance (31%), and number (31%) were the most bothersome cutaneous neurofibroma features. Topical medication (77%–96%), followed by oral medication (54%–93%), was the most preferred treatment modality. Adolescents and caregivers most often replied that cutaneous neurofibroma treatment should be initiated when cutaneous neurofibromas become bothersome. The majority of respondents were willing to treat cutaneous neurofibromas for at least 1 year (64%–75%). Adolescent and caregivers were least willing to risk pain (72%–78%) and nausea/vomiting (59%–81%) as a cutaneous neurofibroma treatment side effect. Conclusions: These data indicate that adolescents with neurofibromatosis 1 are negatively impacted by their cutaneous neurofibromas, and that both adolescents and their caregivers would be willing to try longer-term experimental treatments. [ABSTRACT FROM AUTHOR]

Published
2024
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14. A core outcome domain set to assess cutaneous neurofibromas related to neurofibromatosis type 1 in clinical trials.

Author

Fertitta, Laura, Bergqvist, Christina, Sarin, Kavita Y, Plotkin, Scott R, Moertel, Christopher, Petersen, Andrea K, Cannon, Ashley, Berman, Yemima, Pichard, Dominique C, Röhl, Class, Lessing, Andres, Brizion, Bernadette, Peiffer, Bastien, Ravaud, Philippe, Tran, Viet-Thi, Armand, Marie-Laure, Moryousef, Sabine, Ferkal, Salah, Jannic, Arnaud, and Ezzedine, Khaled

Subjects
NEUROFIBROMATOSIS 1, CLINICAL trials, CONSENSUS (Social sciences), MEDICAL personnel, PATIENT satisfaction
Abstract

Background Cutaneous neurofibromas (cNF) are considered one of the highest burdens of neurofibromatosis type 1 (NF1). To date, no medical treatment can cure cNF or prevent their development. In that context, there is an urgent need to prepare and standardize the methodology of future trials targeting cNF. Objectives The objective was to develop a core outcome domain set suitable for all clinical trials targeting NF1-associated cNF. Methods The validated approach of this work consisted of a three-phase methodology: (i) generating the domains [systematic literature review (SLR) and qualitative studies]; (ii) agreeing (three-round international e-Delphi consensus process and working groups); and (iii) voting. Results (i) The SLR and the qualitative studies (three types of focus groups and a French e-survey with 234 participants) resulted in a preliminary list of 31 candidate items and their corresponding definitions. (ii) A total of 229 individuals from 29 countries participated in the first round of the e-Delphi process: 71 patients, relatives or representatives (31.0%), 130 healthcare professionals (HCPs, 56.8%) and 28 researchers, representatives of a drug regulatory authority, industry or pharmaceutical company representatives or journal editors (12.2%). The overall participation rate was 74%. After round 2, five candidate items were excluded. Between rounds 2 and 3, international workshops were held to better understand the disagreements among stakeholders. This phase led to the identification of 19 items as outcome subdomains. (iii) The items were fused to create four outcome domains ('clinical assessment', 'daily life impact', 'patient satisfaction' and 'perception of health') and prioritized. The seven items that did not reach consensus were marked for the research agenda. The final core outcome domain set reached 100% of the votes of the steering committee members. Conclusions Although numerous outcomes can be explored in studies related to cNF in NF1, the present study offers four outcome domains that should be reported in all trial studies, agreed on by international patients, relatives and representatives of patients; HCPs; researchers, representatives of drug regulatory authorities or pharmaceutical companies and journal editors. The next step will include the development of a set of core outcome measurement instruments to further standardize how these outcomes should be assessed. [ABSTRACT FROM AUTHOR]

Published
2024
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16. sj-pdf-1-ctj-10.1177_17407745231178839 – Supplemental material for Perspectives of adolescents with neurofibromatosis 1 and cutaneous neurofibromas: Implications for clinical trials

Author

Cannon, Ashley, Sarin, Kavita Y, Petersen, Andrea K, Pichard, Dominique C, Wolters, Pamela L, Erickson, Gregg, Lessing, Andrés J, Li, Peng, Röhl, Claas, Rosser, Tena, Widemann, Brigitte C, Blakeley, Jaishri O, and Plotkin, Scott R

Subjects
FOS: Clinical medicine, 160807 Sociological Methodology and Research Methods, 111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified, FOS: Sociology
Abstract

Supplemental material, sj-pdf-1-ctj-10.1177_17407745231178839 for Perspectives of adolescents with neurofibromatosis 1 and cutaneous neurofibromas: Implications for clinical trials by Ashley Cannon, Kavita Y Sarin, Andrea K Petersen, Dominique C Pichard, Pamela L Wolters, Gregg Erickson, Andrés J Lessing, Peng Li, Claas Röhl, Tena Rosser, Brigitte C Widemann, Jaishri O Blakeley and Scott R Plotkin in Clinical Trials

Published
2023
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17. sj-docx-1-ctj-10.1177_17407745231178839 – Supplemental material for Perspectives of adolescents with neurofibromatosis 1 and cutaneous neurofibromas: Implications for clinical trials

Author

Cannon, Ashley, Sarin, Kavita Y, Petersen, Andrea K, Pichard, Dominique C, Wolters, Pamela L, Erickson, Gregg, Lessing, Andrés J, Li, Peng, Röhl, Claas, Rosser, Tena, Widemann, Brigitte C, Blakeley, Jaishri O, and Plotkin, Scott R

Subjects
FOS: Clinical medicine, 160807 Sociological Methodology and Research Methods, 111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified, FOS: Sociology
Abstract

Supplemental material, sj-docx-1-ctj-10.1177_17407745231178839 for Perspectives of adolescents with neurofibromatosis 1 and cutaneous neurofibromas: Implications for clinical trials by Ashley Cannon, Kavita Y Sarin, Andrea K Petersen, Dominique C Pichard, Pamela L Wolters, Gregg Erickson, Andrés J Lessing, Peng Li, Claas Röhl, Tena Rosser, Brigitte C Widemann, Jaishri O Blakeley and Scott R Plotkin in Clinical Trials

Published
2023
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18. SEMA6B variants cause intellectual disability and alter dendritic spine density and axon guidance

Author

Cordovado, Amélie, primary, Schaettin, Martina, additional, Jeanne, Médéric, additional, Panasenkava, Veranika, additional, Denommé-Pichon, Anne-Sophie, additional, Keren, Boris, additional, Mignot, Cyril, additional, Doco-Fenzy, Martine, additional, Rodan, Lance, additional, Ramsey, Keri, additional, Narayanan, Vinodh, additional, Jones, Julie R, additional, Prijoles, Eloise J, additional, Mitchell, Wendy G, additional, Ozmore, Jillian R, additional, Juliette, Kali, additional, Torti, Erin, additional, Normand, Elizabeth A, additional, Granger, Leslie, additional, Petersen, Andrea K, additional, Au, Margaret G, additional, Matheny, Juliann P, additional, Phornphutkul, Chanika, additional, Chambers, Mary-Kathryn, additional, Fernández-Ramos, Joaquín-Alejandro, additional, López-Laso, Eduardo, additional, Kruer, Michael C, additional, Bakhtiari, Somayeh, additional, Zollino, Marcella, additional, Morleo, Manuela, additional, Marangi, Giuseppe, additional, Mei, Davide, additional, Pisano, Tiziana, additional, Guerrini, Renzo, additional, Louie, Raymond J, additional, Childers, Anna, additional, Everman, David B, additional, Isidor, Betrand, additional, Audebert-Bellanger, Séverine, additional, Odent, Sylvie, additional, Bonneau, Dominique, additional, Gilbert-Dussardier, Brigitte, additional, Redon, Richard, additional, Bézieau, Stéphane, additional, Laumonnier, Frédéric, additional, Stoeckli, Esther T, additional, Toutain, Annick, additional, and Vuillaume, Marie-Laure, additional

Published
2022
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20. Diagnostic Yield of Clinical Tumor and Germline Whole-Exome Sequencing for Children With Solid Tumors

Author

Parsons, D. Williams, Roy, Angshumoy, Yang, Yaping, Wang, Tao, Scollon, Sarah, Bergstrom, Katie, Kerstein, Robin A., Gutierrez, Stephanie, Petersen, Andrea K., Bavle, Abhishek, Lin, Frank Y., López-Terrada, Dolores H., Monzon, Federico A., Hicks, M. John, Eldin, Karen W., Quintanilla, Norma M., Adesina, Adekunle M., Mohila, Carrie A., Whitehead, William, Jea, Andrew, Vasudevan, Sanjeev A., Nuchtern, Jed G., Ramamurthy, Uma, McGuire, Amy L., Hilsenbeck, Susan G., Reid, Jeffrey G., Muzny, Donna M., Wheeler, David A., Berg, Stacey L., Chintagumpala, Murali M., Eng, Christine M., Gibbs, Richard A., and Plon, Sharon E.

Published
2016
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21. Mutation-specific pathophysiological mechanisms define different neurodevelopmental disorders associated with SATB1 dysfunction

Author

den Hoed, Joery, de Boer, Elke, Voisin, N, Dingemans, A, Guex, N, Wiel, L, Nellaker, C, Amudhavalli, S, Banka, S, Bena, F, Ben-Zeev, B, Bonagura, V, Bruel, A, Brunet, T, Brunner, H. G., Chew, H. B., Chrast, J., Cimbalistienė, Loreta, Coon, Hilary, study, The DDD, Délot, Emmanuèlle C, Démurger, Florence, Denommé-Pichon, Anne-Sophie, Depienne, C., Donnai, Dian, Dyment, David A, Elpeleg, Orly, Faivre, L, Gilissen, Christian, Granger, L., Haber, Benjamin, Hachiya, Yasuo, Abedi, Yasmin Hamzavi, Hanebeck, Jennifer, Hehir-Kwa, Jayne Y, Horist, Brooke, Itai, Toshiyuki, Jackson, Adam, Jewell, Rosalyn, Jones, Kelly L., Joss, Shelagh, Kashii, Hirofumi, Kato, Mitsuhiro, Kattentidt-Mouravieva, Anja A, Kok, Fernando, Kotzaeridou, Urania, Krishnamurthy, Vidya, Kučinskas, Vaidutis, Kuechler, Alma, Lavillaureix, Alinoë, Liu, Pengfei, Manwaring, Linda, Matsumoto, Naomichi, Mazel, Benoît, McWalter, Kirsty, Meiner, Vardiella, Mikati, Mohamad A., Miyatake, Satoko, Mizuguchi, Takeshi, Moey, Lip H., Mohammed, Shehla, Mor-Shaked, Hagar, Mountford, Hayley, Newbury-Ecob, Ruth, Odent, Sylvie, Orec, Laura, Osmond, Matthew, Palculict, Timothy Blake, Parker, Michael, Petersen, Andrea K., Pfundt, Rolph, Preikšaitienė, Eglė, Radtke, Kelly, Ranza, Emmanuelle, Rosenfeld, Jill A., Santiago-Sim, Teresa, Schwager, Caitlin, Sinnema, Margje, Blok, Lot Snijders, Spillmann, Rebecca C., Stegmann, Alexander P A, Thiffault, Isabelle, Tran, Linh, Vaknin-Dembinsky, Adi, Vedovato-dos-Santos, Juliana H., Schrier Vergano, Samantha A., Vilain, Eric, Vitobello, Antonio, Wagner, Matias, Waheeb, Androu, Willing, Marcia C., Zuccarelli, Britton D, Kini, Usha, Newbury, Dianne F., Kleefstra, Tjitske, Reymond, Alexandre, Fisher, Simon E., and Vissers, Lisenka E L M

Abstract

Whereas large-scale statistical analyses can robustly identify disease-gene relationships, they do not accurately capture genotype-phenotype correlations or disease mechanisms. We use multiple lines of independent evidence to show that different variant types in a single gene, SATB1, cause clinically overlapping but distinct neurodevelopmental disorders. Clinical evaluation of 42 individuals carrying SATB1 variants identified overt genotype-phenotype relationships, associated with different pathophysiological mechanisms, established by functional assays. Missense variants in the CUT1 and CUT2 DNA-binding domains result in stronger chromatin binding, increased transcriptional repression and a severe phenotype. Contrastingly, variants predicted to result in haploinsufficiency are associated with a milder clinical presentation. A similarly mild phenotype is observed for individuals with premature protein truncating variants that escape nonsense-mediated decay and encode truncated proteins, which are transcriptionally active but mislocalized in the cell. Our results suggest that in-depth mutation-specific genotype-phenotype studies are essential to capture full disease complexity and to explain phenotypic variability.

Published
2020
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22. Therapies Harness Power of Positivity

Author

Petersen, Andrea

Subjects
Mental health, Psychologists, Health, General interest, News, opinion and commentary
Abstract

Anne Firmender, 74, was working with her psychologist to come up with a list of her positive attributes. ''I cook for others,'' said Ms. Firmender. ''It's giving,'' encouraged the psychologist, [...]

Published
2019

25. What's Missing? Towels and Toilet Paper, for Starters

Author

Petersen, Andrea

Subjects
Vacation homes -- Forecasts and trends -- Surveys, Customer satisfaction -- Forecasts and trends -- Surveys, Online information services -- Services -- Surveys, Beauty salons, Market trend/market analysis, Online information service, General interest, News, opinion and commentary
Abstract

When Chelle Neff and her husband, David Neff, traveled from their home in Austin, Tex., to Dallas to visit family over Christmas, they stayed in a one-bedroom loft they rented [...]

Published
2019

26. Homozygous Missense Variants in NTNG2, Encoding a Presynaptic Netrin-G2 Adhesion Protein, Lead to a Distinct Neurodevelopmental Disorder

Author

Dias, Caroline M., primary, Punetha, Jaya, additional, Zheng, Céline, additional, Mazaheri, Neda, additional, Rad, Abolfazl, additional, Efthymiou, Stephanie, additional, Petersen, Andrea, additional, Dehghani, Mohammadreza, additional, Pehlivan, Davut, additional, Partlow, Jennifer N., additional, Posey, Jennifer E., additional, Salpietro, Vincenzo, additional, Gezdirici, Alper, additional, Malamiri, Reza Azizi, additional, Al Menabawy, Nihal M., additional, Selim, Laila A., additional, Vahidi Mehrjardi, Mohammad Yahya, additional, Banu, Selina, additional, Polla, Daniel L., additional, Yang, Edward, additional, Rezazadeh Varaghchi, Jamileh, additional, Mitani, Tadahiro, additional, van Beusekom, Ellen, additional, Najafi, Maryam, additional, Sedaghat, Alireza, additional, Keller-Ramey, Jennifer, additional, Durham, Leslie, additional, Coban-Akdemir, Zeynep, additional, Karaca, Ender, additional, Orlova, Valeria, additional, Schaeken, Lieke L.M., additional, Sherafat, Amir, additional, Jhangiani, Shalini N., additional, Stanley, Valentina, additional, Shariati, Gholamreza, additional, Galehdari, Hamid, additional, Gleeson, Joseph G., additional, Walsh, Christopher A., additional, Lupski, James R., additional, Seiradake, Elena, additional, Houlden, Henry, additional, van Bokhoven, Hans, additional, and Maroofian, Reza, additional

Published
2019
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27. Cover Image, Volume 40, Issue 3

Author

Rehman, Atteeq U., primary, Najafi, Maryam, additional, Kambouris, Marios, additional, Al-Gazali, Lihadh, additional, Makrythanasis, Periklis, additional, Rad, Abolfazl, additional, Maroofian, Reza, additional, Rajab, Anna, additional, Stark, Zornitza, additional, Hunter, Jill V., additional, Bakey, Zeineb, additional, Tokita, Mari J., additional, He, Weimin, additional, Vetrini, Francesco, additional, Petersen, Andrea, additional, Santoni, Federico A., additional, Hamamy, Hanan, additional, Wu, Kaman, additional, Al-Jasmi, Fatma, additional, Helmstädter, Martin, additional, Arnold, Sebastian J., additional, Xia, Fan, additional, Richmond, Christopher, additional, Liu, Pengfei, additional, Karimiani, Ehsan Ghayoor, additional, Karami Madani, GholamReza, additional, Lunke, Sebastian, additional, El-Shanti, Hatem, additional, Eng, Christine M., additional, Antonarakis, Stylianos E., additional, Hertecant, Jozef, additional, Walkiewicz, Magdalena, additional, Yang, Yaping, additional, and Schmidts, Miriam, additional

Published
2019
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28. Biallelic loss of function variants in PPP1R21 cause a neurodevelopmental syndrome with impaired endocytic function

Author

Rehman, Atteeq U., primary, Najafi, Maryam, additional, Kambouris, Marios, additional, Gazali, Lihadh Al, additional, Makrythanasis, Periklis, additional, Rad, Abolfazl, additional, Maroofian, Reza, additional, Rajab, Anna, additional, Stark, Zornitza, additional, Hunter, Jill V., additional, Bakey, Zeineb, additional, Tokita, Mari J., additional, He, Weimin, additional, Vetrini, Francesco, additional, Petersen, Andrea, additional, Santoni, Federico A., additional, Hamamy, Hanan, additional, Wu, Kaman, additional, Jasmi, Fatma Al, additional, Helmstädter, Martin, additional, Arnold, Sebastian J., additional, Xia, Fan, additional, Richmond, Christopher, additional, Liu, Pengfei, additional, Karimiani, Ehsan Ghayoor, additional, Madani, GholamReza Karami, additional, Lunke, Sebastian, additional, El‐Shanti, Hatem, additional, Eng, Christine M., additional, Antonarakis, Stylianos E., additional, Hertecant, Jozef, additional, Walkiewicz, Magdalena, additional, Yang, Yaping, additional, and Schmidts, Miriam, additional

Published
2018
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30. Why Do Men Eat So Much Meat?

Author

Petersen, Andrea

Subjects
*MEN'S health, *MIDDLE-aged men, *PORK, *HIGH-protein diet, *MEAT cuts
Abstract

American men have a tendency to consume excessive amounts of meat, particularly red and processed meat, despite the health risks associated with it. Research has linked overindulgence in meat to heart disease, stroke, certain types of cancers, and diabetes. Men's love for meat is often associated with notions of strength and power, and some studies have found that men with more traditional views of masculinity tend to eat more meat. While meat does provide certain nutritional benefits, it is important to consume it in moderation and choose unprocessed options over processed ones. [Extracted from the article]

Published
2024

31. Short-Term Therapy Programs for Quick Relief

Author

Petersen, Andrea

Subjects
Obsessive compulsive disorder -- Care and treatment, Child mental health -- Care and treatment, Psychotherapy -- Methods, General interest, News, opinion and commentary
Abstract

Six middle- and high-school students sat around a table on a Monday afternoon, watching a psychologist write three letters on a whiteboard: O-C-D. ''What does O.C.D. stand for?'' the psychologist, [...]

Published
2018

33. How Much Dairy in Your Diet is Healthy?

Author

Petersen, Andrea

Subjects
*DIETARY calcium, *DAIRY products, *BOK choy, *CANCER cell growth, *TYPE 2 diabetes
Abstract

A growing number of researchers and doctors are challenging the traditional advice to consume multiple servings of dairy products per day. The U.S. government is reevaluating its recommendation of three servings of dairy a day, as some studies have linked dairy-rich diets to increased risks of cardiovascular disease and certain cancers. However, the research on dairy is not clear-cut, with some studies suggesting that dairy foods may lower the risk of heart disease, certain cancers, and Type 2 diabetes. Nutrition experts suggest that one serving of dairy per day is sufficient, and calcium can also be obtained from other sources like fortified soy milk, tofu, kale, edamame, and bok choy. The debate between low-fat and full-fat dairy products continues, with some studies finding little difference in health outcomes. Ultimately, individuals should choose the fat level they prefer, but those with high cholesterol may want to stick with low-fat options. Yogurt is considered a healthy choice of dairy food, as it contains probiotics that can improve gut health. [Extracted from the article]

Published
2024

36. Die Bedeutung von sozialer Unterstützung und Arbeitsengagement für die Arbeitsleistung

Author

Petersen, Andrea

Abstract

Die heutige Arbeitswelt befindet sich in einem raschen Wandel, was mit Veränderungen für Organisationen und Angestellte verbunden ist. Gleichzeitig erfordert der vorherrschende wirtschaftliche Druck besondere Leistungen und Einsatz der Angestellten um als Organisation wettbewerbsfähig zu bleiben. Dabei spielen die Arbeitsressourcen und das Arbeitsengagement der Angestellten eine wesentliche Bedeutung. In der vorliegenden Studie wurde der Einfluss von sozialer Unterstützung durch KollegInnen, direkte Vorgesetzte und Vorgesetzte höherer Ebenen auf das Arbeitsengagement und die Arbeitsleistung untersucht. Es wurde auf Grundlage des Job Demands-Resourcen Modells und der sozialen Austauschtheorie untersucht, ob Arbeitsengagement den Zusammenhang von sozialer Unterstützung der drei Bezugsgruppen auf die Arbeitsleistung mediiert. Dazu wurde eine längsschnittliche Untersuchung zu drei Erhebungszeitpunkten durchgeführt. Erhoben wurden die Daten mittels eines Fragebogens, der in einer online und einer Papier-Bleistift-Version vorlag und mittels Schneeballsystem versandt wurde. Es wurden Daten von 262 Personen, die zu allen drei Erhebungszeitpunkten teilgenommen haben, verwendet. Die Hypothesen wurden mittels Mediationsanalysen analysiert. Die Ergebnisse der vorliegenden Studie zeigten keine signifikanten Effekte. Alle untersuchten Hypothesen mussten leider entgegen der theoretischen Annahmen dieser und anderer Arbeiten verworfen werden. Eine mögliche Erklärung dafür ist, dass Arbeitsengagement und Arbeitsressourcen als stabile Konstrukte gelten und dass die Formulierungen der Fragestellungen der vorliegenden Studie diese Problematik begünstigt haben könnten. Die theoretischen Annahmen der vorliegenden Arbeit können trotzdem als praxisrelevant angesehen werden und es kann für zukünftige Forschungen angenommen werden, dass das Überwinden der methodischen Probleme dieser Arbeit zu signifikanten Ergebnissen führt., In today’s world where the economic pressures on companies are high, the work environment in these companies is also undergoing a rapid change. Employers as well as their employees are in constant demand to achieve a high work performance in order for the organisation/company to be successful. In this regard, job resources and work engagement of employees are important issues, because they have an impact on an employee’s work performance. On the basis of the job demands-resources model and the social exchange theory, the present study examined whether the relationship between job resources and work performance was mediated by the employee ́s work engagement. To address this question, a longitudinal research design with three points of data conduction was used. The data acquisition instrument was a questionnaire, which was made available either online or as a printed version and it was further sent in a “snowball system”. Data from 262 participants, who filled the questionnaire at all three points of conduction, was used for analysis of the hypotheses; which was further tested in a mediation analysis. The results of the present study were found to be non- significant, against the theory of the present study, as well as theories of previous studies. Therefore, all hypotheses had to be rejected. A possible explanation for these outcomes, might be that work engagement and job resources were found to be stable constructs over time and that the items used in the present study are expressed in a beneficial way towards the stability problem. Nevertheless, the theoretical assumptions of the present study have important practical implications and furthermore, it is assumed that the conclusions of the methodological problems of the present study lead toward obtaining significant results in future research.

Published
2015
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37. Biallelic loss of function variants in PPP1R21 cause a neurodevelopmental syndrome with impaired endocytic function.

Author

Rehman, Atteeq U., Najafi, Maryam, Kambouris, Marios, Al‐Gazali, Lihadh, Makrythanasis, Periklis, Rad, Abolfazl, Maroofian, Reza, Rajab, Anna, Stark, Zornitza, Hunter, Jill V., Bakey, Zeineb, Tokita, Mari J., He, Weimin, Vetrini, Francesco, Petersen, Andrea, Santoni, Federico A., Hamamy, Hanan, Wu, Kaman, Al‐Jasmi, Fatma, and Helmstädter, Martin

Abstract

Next‐generation sequencing (NGS) has been instrumental in solving the genetic basis of rare inherited diseases, especially neurodevelopmental syndromes. However, functional workup is essential for precise phenotype definition and to understand the underlying disease mechanisms. Using whole exome (WES) and whole genome sequencing (WGS) in four independent families with hypotonia, neurodevelopmental delay, facial dysmorphism, loss of white matter, and thinning of the corpus callosum, we identified four previously unreported homozygous truncating PPP1R21 alleles: c.347delT p.(Ile116Lysfs*25), c.2170_2171insGGTA p.(Ile724Argfs*8), c.1607dupT p.(Leu536Phefs*7), c.2063delA p.(Lys688Serfs*26) and found that PPP1R21 was absent in fibroblasts of an affected individual, supporting the allele's loss of function effect. PPP1R21 function had not been studied except that a large scale affinity proteomics approach suggested an interaction with PIBF1 defective in Joubert syndrome. Our co‐immunoprecipitation studies did not confirm this but in contrast defined the localization of PPP1R21 to the early endosome. Consistent with the subcellular expression pattern and the clinical phenotype exhibiting features of storage diseases, we found patient fibroblasts exhibited a delay in clearance of transferrin‐488 while uptake was normal. In summary, we delineate a novel neurodevelopmental syndrome caused by biallelic PPP1R21 loss of function variants, and suggest a role of PPP1R21 within the endosomal sorting process or endosome maturation pathway. We describe PPP1R21 loss of function in 4 independent families with syndromal neurodevelopmental delay by exome and genome sequencing. Immunoflorescence analysis reveals wildtype PPP1R21 localises to the early endosome and PPP1R21 loss of function in patient fibroblasts results in disturbances of the endosomal sorting process or endosome maturation pathway. [ABSTRACT FROM AUTHOR]

Published
2019
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39. Would Nutrition Labels on the Front of Food Packages Make You Eat Healthier?

Author

Petersen, Andrea and Newman, Jesse

Subjects
*FOOD labeling, *NUTRITION, *EMERGING markets, *GOVERNMENT policy
Abstract

The Food and Drug Administration (FDA) is considering requiring food manufacturers to put new labels on the front of packages in an effort to improve American eating habits. These labels would flag certain health risks, such as high levels of salt, sugar, or saturated fat. The food industry is pushing back, claiming that there isn't enough evidence that labels can significantly change consumer behavior. However, research has shown that front-of-package nutrition labels in countries like Chile and Mexico have led to changes in consumer choices and even prompted food manufacturers to make their products healthier. [Extracted from the article]

Published
2024

40. The New Science on What Ultra-Processed Food Does to Your Brain.

Author

Petersen, Andrea

Subjects
*COMPULSIVE behavior, *SLEEP disorders
Abstract

New research suggests that ultra-processed foods, such as chips and packaged snacks, may not only affect our bodies but also our brains. These foods can act like addictive substances, leading to changes in the way we learn, remember, and feel. Some scientists are even proposing a new mental-health condition called "ultra-processed food use disorder." While the science is still early and not all ultra-processed foods are equal, diets high in these foods have been linked to obesity, Type 2 diabetes, cancer, cardiovascular disease, and mental health and sleep problems. The combination of high levels of fat and carbs in many ultra-processed foods, along with their rapid impact on the brain's reward system, may contribute to their addictive nature. Additionally, the gut microbiome and changes in the brain's reward system caused by these foods could also affect mental health. [Extracted from the article]

Published
2024

44. HOW TO FIND A THERAPIST.

Author

Petersen, Andrea

Subjects
ANXIETY treatment, MENTAL depression, PSYCHIATRISTS, PSYCHOLOGISTS, COUNSELORS
Abstract

The article provides suggestions for finding an appropriate therapist. Topics discussed include information offered by the Anxiety and Depression Association of America (ADAA) regarding percentage of people receiving treatment for anxiety; information on several therapists like psychiatrists, psychologists and social workers, counselors, and marriage and family therapists; and suggestions for dealing with financial issues.

Published
2018

45. What, Exactly, Should You Eat? It's a $190 Million Question.

Author

Petersen, Andrea

Subjects
*NUTRITION
Abstract

The National Institutes of Health (NIH) is conducting a $189 million study involving 10,000 participants to investigate how different diets affect individuals. The study aims to develop personalized nutrition advice by collecting vast amounts of data and creating algorithms to predict the effects of specific diets. Participants will spend two weeks each on three different diets, and scientists will measure various metrics, such as insulin and glucose levels, to determine individual responses. The study hopes to provide more customized guidance to help Americans improve their health and adhere to healthier diets. [Extracted from the article]

Published
2024

46. The Healthiest Oils to Cook With, According to Experts.

Author

Petersen, Andrea

Subjects
*DIETARY fats, *CHEMICAL processes, *OMEGA-6 fatty acids, *CORN oil, *SAFFLOWER oil
Abstract

The article discusses the debate surrounding the healthiest oils to cook with. While there are many options available, experts generally recommend olive oil and avocado oil due to their healthy unsaturated fats and minimal processing. These oils are considered to be better choices compared to seed oils like canola, corn, soybean, and sunflower oil, which are often labeled as "toxic" on social media platforms. However, seed oils are rich in unsaturated fats that are linked to good health. The article also mentions concerns about oils with a high percentage of omega-6 fatty acids, as they can cause inflammation in some individuals. Overall, experts emphasize that the overall diet and consumption of ultra-processed foods are more important factors to consider for health than the specific oil used for cooking. [Extracted from the article]

Published
2024

47. Trying to Eat Healthier This Year? Eat Less Sugar With These Tips.

Author

Petersen, Andrea

Subjects
*FOOD portions, *SUGARS, *TYPE 2 diabetes, *SUGAR, *ESSENTIAL nutrients, *DAIRY products
Abstract

Reducing sugar intake is an important strategy for good health, as diets high in added sugars are linked to obesity and Type 2 diabetes. While guidelines recommend limiting added sugar consumption to 10% of daily calories, Americans still consume an average of 13% of their daily calories from added sugars. It is important to distinguish between added sugars found in processed foods and sugar that occurs naturally in foods like fruit and dairy products, which provide necessary nutrients. Strategies to reduce added sugar intake include reading nutrition labels, avoiding sugar-sweetened beverages, visualizing teaspoons of sugar, and adjusting portion sizes and frequency of desserts and sweet snacks. [Extracted from the article]

Published
2024

48. Diet Company Medifast, Once an Ozempic Skeptic, Embraces Weight Loss Drugs With LifeMD Telehealth Deal.

Author

Petersen, Andrea

Subjects
*ANTIOBESITY agents, *SEMAGLUTIDE, *TELEMEDICINE, *DIET, *FOOD habits
Abstract

Medifast, a weight-loss company known for its non-drug approach, is investing $20 million in telehealth provider LifeMD to give its customers access to doctors who can prescribe weight-loss medications like Ozempic and Wegovy. This move comes after Medifast's Optavia coaching and food program generated $1.6 billion in revenue in 2022, but struggled to acquire new customers as GLP-1 medications gained popularity. Medifast had previously expressed concerns about the medications' side effects and long-term effects, but now believes they can be safe and effective when combined with healthy eating and exercise. Other weight-loss companies, such as WeightWatchers and Noom, have also entered the market for weight-loss medications. [Extracted from the article]

Published
2023

49. Diagnostic Yield of Clinical Tumor and Germline Whole-Exome Sequencing for Children With Solid Tumors.

Author

Williams Parsons, D., Roy, Angshumoy, Yaping Yang, Tao Wang, Scollon, Sarah, Bergstrom, Katie, Kerstein, Robin A., Gutierrez, Stephanie, Petersen, Andrea K., Bavle, Abhishek, Lin, Frank Y., López-Terrada, Dolores H., Monzon, Federico A., John Hicks, M., Eldin, Karen W., Quintanilla, Norma M., Adesina, Adekunle M., Mohila, Carrie A., Whitehead, William, and Jea, Andrew

Published
2016
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50. Man who cloned cat has new cause: menopausual women; Mr. Sperling spends millions challenging NIH study on hormone replacement

Author

Petersen, Andrea

Subjects
United States. National Institutes of Health -- Research, United States. National Institutes of Health -- Reports, Menopause -- Research, Hormone therapy -- Research, Hormone therapy -- Reports, Hormone therapy -- Analysis, Cloning -- Research, Billionaires -- Management, Billionaires -- Research, Company business management, News, opinion and commentary
Published
2004

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