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569 results on '"Palmer, Elizabeth"'

1. De novo variants in the RNU4-2 snRNA cause a frequent neurodevelopmental syndrome.

Author

Chen, Yuyang, Dawes, Ruebena, Kim, Hyung, Ljungdahl, Alicia, Stenton, Sarah, Walker, Susan, Lord, Jenny, Lemire, Gabrielle, Martin-Geary, Alexandra, Ganesh, Vijay, Ma, Jialan, Ellingford, Jamie, Delage, Erwan, DSouza, Elston, Dong, Shan, Adams, David, Allan, Kirsten, Bakshi, Madhura, Baldwin, Erin, Berger, Seth, Bernstein, Jonathan, Bhatnagar, Ishita, Blair, Ed, Brown, Natasha, Burrage, Lindsay, Chapman, Kimberly, Coman, David, Compton, Alison, Cunningham, Chloe, DSouza, Precilla, Danecek, Petr, Délot, Emmanuèle, Dias, Kerith-Rae, Elias, Ellen, Elmslie, Frances, Evans, Care-Anne, Ewans, Lisa, Ezell, Kimberly, Fraser, Jamie, Gallacher, Lyndon, Genetti, Casie, Goriely, Anne, Grant, Christina, Haack, Tobias, Higgs, Jenny, Hinch, Anjali, Hurles, Matthew, Kuechler, Alma, Lachlan, Katherine, Lalani, Seema, Lecoquierre, François, Leitão, Elsa, Fevre, Anna, Leventer, Richard, Liebelt, Jan, Lindsay, Sarah, Lockhart, Paul, Ma, Alan, Macnamara, Ellen, Mansour, Sahar, Maurer, Taylor, Mendez, Hector, Metcalfe, Kay, Montgomery, Stephen, Moosajee, Mariya, Nassogne, Marie-Cécile, Neumann, Serena, ODonoghue, Michael, OLeary, Melanie, Palmer, Elizabeth, Pattani, Nikhil, Phillips, John, Pitsava, Georgia, Pysar, Ryan, Rehm, Heidi, Reuter, Chloe, Revencu, Nicole, Riess, Angelika, Rius, Rocio, Rodan, Lance, Roscioli, Tony, Rosenfeld, Jill, Sachdev, Rani, Shaw-Smith, Charles, Simons, Cas, Sisodiya, Sanjay, Snell, Penny, St Clair, Laura, Stark, Zornitza, Stewart, Helen, Tan, Tiong, Tan, Natalie, Temple, Suzanna, Thorburn, David, Tifft, Cynthia, Uebergang, Eloise, VanNoy, Grace, Vasudevan, Pradeep, Vilain, Eric, and Viskochil, David

Subjects
Humans, RNA, Small Nuclear, Neurodevelopmental Disorders, Female, Male, Brain, Heterozygote, Alleles, Syndrome, Spliceosomes, Animals
Abstract

Around 60% of individuals with neurodevelopmental disorders (NDD) remain undiagnosed after comprehensive genetic testing, primarily of protein-coding genes1. Large genome-sequenced cohorts are improving our ability to discover new diagnoses in the non-coding genome. Here we identify the non-coding RNA RNU4-2 as a syndromic NDD gene. RNU4-2 encodes the U4 small nuclear RNA (snRNA), which is a critical component of the U4/U6.U5 tri-snRNP complex of the major spliceosome2. We identify an 18 base pair region of RNU4-2 mapping to two structural elements in the U4/U6 snRNA duplex (the T-loop and stem III) that is severely depleted of variation in the general population, but in which we identify heterozygous variants in 115 individuals with NDD. Most individuals (77.4%) have the same highly recurrent single base insertion (n.64_65insT). In 54 individuals in whom it could be determined, the de novo variants were all on the maternal allele. We demonstrate that RNU4-2 is highly expressed in the developing human brain, in contrast to RNU4-1 and other U4 homologues. Using RNA sequencing, we show how 5 splice-site use is systematically disrupted in individuals with RNU4-2 variants, consistent with the known role of this region during spliceosome activation. Finally, we estimate that variants in this 18 base pair region explain 0.4% of individuals with NDD. This work underscores the importance of non-coding genes in rare disorders and will provide a diagnosis to thousands of individuals with NDD worldwide.

Published
2024

2. Pushing the boundaries of rare disease diagnostics with the help of the first Undiagnosed Hackathon

Author

Delgado-Vega, Angelica Maria, Cederroth, Helene, Taylan, Fulya, Ekholm, Katja, Ek, Marlene, Thonberg, Håkan, Jemt, Anders, Nilsson, Daniel, Eisfeldt, Jesper, Bilgrav Saether, Kristine, Höijer, Ida, Akgun-Dogan, Ozlem, Asano, Yui, Barakat, Tahsin Stefan, Batkovskyte, Dominyka, Baynam, Gareth, Bodamer, Olaf, Chetruengchai, Wanna, Corcoran, Pádraic, Couse, Madeline, Danis, Daniel, Demidov, German, Dohi, Eisuke, Erhardsson, Mattias, Fernandez-Luna, Luis, Fujiwara, Toyofumi, Garg, Neha, Giugliani, Roberto, Gonzaga-Jauregui, Claudia, Grigelioniene, Giedre, Groza, Tudor, Gunnarsson, Cecilia, Hammarsjö, Anna, Hammond, Charles Kumi, Hatirnaz Ng, Özden, Hesketh, Sirisha, Hettiarachchi, Dineshani, Johansson Soller, Maria, Kirmani, Umn Ahmed, Kjellberg, Martin, Kvarnung, Malin, Kvlividze, Oleg, Lagerstedt-Robinson, Kristina, Lasko, Paul, Lassmann, Timo, Lau, Lynette Y. S., Laurie, Steven, Lim, Weng Khong, Liu, Zhandong, Lysenkova Wiklander, Mariya, Makay, Prince, Maiga, Alassane Baneye, Maya-González, Carolina, Meyn, M. Stephen, Neethiraj, Ramprasad, Nigro, Vincenzo, Nordgren, Felix, Nordlund, Jessica, Orrsjö, Sara, Ottosson, Jesper, Ozbek, Ugur, Özdemir, Özkan, Partin, Clyde, Pearce, David A., Peck, Raquel, Pedersen, Annie, Pettersson, Maria, Pongpanich, Monnat, Posada de la Paz, Manuel, Ramani, Arun, Romero, Juan Andres, Romero, Vanessa I., Rosenquist, Richard, Saw, Aung Min, Spencer, Matthew, Stattin, Eva-Lena, Srichomthong, Chalurmpon, Tapia-Paez, Isabel, Taruscio, Domenica, Taylor, Julie P., Tkemaladze, Tinatin, Tully, Ian, Tümer, Zeynep, van Zelst-Stams, Wendy A. G., Verloes, Alain, Västerviga, Emma, Wang, Sailan, Yang, Rachel, Yamamoto, Shinya, Yépez, Vicente A., Zhang, Qing, Shotelersuk, Vorasuk, Wiafe, Samuel Agyei, Alanay, Yasemin, Botto, Lorenzo D., Kirmani, Salman, Lumaka, Aimé, Palmer, Elizabeth Emma, Puri, Ratna Dua, Wirta, Valtteri, Lindstrand, Anna, Buske, Orion J., Cederroth, Mikk, and Nordgren, Ann

Published
2024
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5. Functional and clinical studies reveal pathophysiological complexity of CLCN4-related neurodevelopmental condition.

Author

Palmer, Elizabeth, Pusch, Michael, Picollo, Alessandra, Forwood, Caitlin, Nguyen, Matthew, Suckow, Vanessa, Gibbons, Jessica, Hoff, Alva, Sigfrid, Lisa, Megarbane, Andre, Nizon, Mathilde, Cogné, Benjamin, Beneteau, Claire, Alkuraya, Fowzan, Chedrawi, Aziza, Hashem, Mais, Stamberger, Hannah, Weckhuysen, Sarah, Vanlander, Arnaud, Ceulemans, Berten, Rajagopalan, Sulekha, Nunn, Kenneth, Arpin, Stéphanie, Raynaud, Martine, Motter, Constance, Ward-Melver, Catherine, Janssens, Katrien, Meuwissen, Marije, Beysen, Diane, Dikow, Nicola, Grimmel, Mona, Haack, Tobias, Clement, Emma, McTague, Amy, Hunt, David, Townshend, Sharron, Ward, Michelle, Richards, Linda, Simons, Cas, Costain, Gregory, Dupuis, Lucie, Mendoza-Londono, Roberto, Dudding-Byth, Tracy, Boyle, Jackie, Saunders, Carol, Fleming, Emily, El Chehadeh, Salima, Spitz, Marie-Aude, Piton, Amelie, Gerard, Bénédicte, Abi Warde, Marie-Thérèse, Rea, Gillian, McKenna, Caoimhe, Douzgou, Sofia, Banka, Siddharth, Akman, Cigdem, Bain, Jennifer, Sands, Tristan, Wilson, Golder, Silvertooth, Erin, Miller, Lauren, Lederer, Damien, Sachdev, Rani, Macintosh, Rebecca, Monestier, Olivier, Karadurmus, Deniz, Collins, Felicity, Carter, Melissa, Rohena, Luis, Willemsen, Marjolein, Ockeloen, Charlotte, Pfundt, Rolph, Kroft, Sanne, Field, Michael, Laranjeira, Francisco, Fortuna, Ana, Soares, Ana, Michaud, Vincent, Naudion, Sophie, Golla, Sailaja, Weaver, David, Bird, Lynne, Friedman, Jennifer, Clowes, Virginia, Joss, Shelagh, Pölsler, Laura, Campeau, Philippe, Blazo, Maria, Bijlsma, Emilia, Rosenfeld, Jill, Beetz, Christian, Powis, Zöe, McWalter, Kirsty, Brandt, Tracy, Torti, Erin, Mathot, Mikaël, Mohammad, Shekeeb, Armstrong, Ruth, and Kalscheuer, Vera

Subjects
Male, Female, Humans, Neurodevelopmental Disorders, Mutation, Missense, Genes, X-Linked, Phenotype, Chloride Channels
Abstract

Missense and truncating variants in the X-chromosome-linked CLCN4 gene, resulting in reduced or complete loss-of-function (LOF) of the encoded chloride/proton exchanger ClC-4, were recently demonstrated to cause a neurocognitive phenotype in both males and females. Through international clinical matchmaking and interrogation of public variant databases we assembled a database of 90 rare CLCN4 missense variants in 90 families: 41 unique and 18 recurrent variants in 49 families. For 43 families, including 22 males and 33 females, we collated detailed clinical and segregation data. To confirm causality of variants and to obtain insight into disease mechanisms, we investigated the effect on electrophysiological properties of 59 of the variants in Xenopus oocytes using extended voltage and pH ranges. Detailed analyses revealed new pathophysiological mechanisms: 25% (15/59) of variants demonstrated LOF, characterized by a shift of the voltage-dependent activation to more positive voltages, and nine variants resulted in a toxic gain-of-function, associated with a disrupted gate allowing inward transport at negative voltages. Functional results were not always in line with in silico pathogenicity scores, highlighting the complexity of pathogenicity assessment for accurate genetic counselling. The complex neurocognitive and psychiatric manifestations of this condition, and hitherto under-recognized impacts on growth, gastrointestinal function, and motor control are discussed. Including published cases, we summarize features in 122 individuals from 67 families with CLCN4-related neurodevelopmental condition and suggest future research directions with the aim of improving the integrated care for individuals with this diagnosis.

Published
2023

8. 'I Didn't Know This Was Actually Stuff That Could Help Us, with Actually Learning': Student Perceptions of Active Blended Learning

Author

Lomer, Sylvie and Palmer, Elizabeth

Abstract

This paper analyses student perceptions of Active Blended Learning (ABL) during the transition to an institutional pedagogy at the University of Northampton. In focus groups with 227 student participants across all four faculties, we explored factors mediating student engagement with ABL. Students expressed a preference for face to face teaching and perceived an increase in expectations of independent learning. Students challenged the relationship between online components and assessment. Consumerist narratives were a consistent thread, with online learning perceived as offering less value for money. Although the lecturers self-reported as having fully implemented ABL, the students' descriptions suggested that learning was not always active, with blended learning often a bolt-on to traditional classroom practice.

Published
2023
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9. PhenoScore quantifies phenotypic variation for rare genetic diseases by combining facial analysis with other clinical features using a machine-learning framework

Author

Dingemans, Alexander J. M., Hinne, Max, Truijen, Kim M. G., Goltstein, Lia, van Reeuwijk, Jeroen, de Leeuw, Nicole, Schuurs-Hoeijmakers, Janneke, Pfundt, Rolph, Diets, Illja J., den Hoed, Joery, de Boer, Elke, Coenen-van der Spek, Jet, Jansen, Sandra, van Bon, Bregje W., Jonis, Noraly, Ockeloen, Charlotte W., Vulto-van Silfhout, Anneke T., Kleefstra, Tjitske, Koolen, David A., Campeau, Philippe M., Palmer, Elizabeth E., Van Esch, Hilde, Lyon, Gholson J., Alkuraya, Fowzan S., Rauch, Anita, Marom, Ronit, Baralle, Diana, van der Sluijs, Pleuntje J., Santen, Gijs W. E., Kooy, R. Frank, van Gerven, Marcel A. J., Vissers, Lisenka E. L. M., and de Vries, Bert B. A.

Published
2023
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11. Grounded Framework for Culturally Relevant and Responsive Music Teaching

Author

Palmer, Elizabeth S., Vodicka, Jason, Huynh, Tina, D'Alexander, Christine, and Crawford, Lisa

Abstract

Building upon the work of Ladson-Billings, Lind and McKoy, and Shaw, our proposed framework takes into consideration the depth and breadth of musical experiences and contexts, musical content, and the diversity of musical cultures. The proposed framework includes four quadrants: (a) teacher competencies, (b) informed choices, (c) authenticity, and (d) holistic and comparative lessons. The framework provides K-16 teachers with tangible, accessible, and actionable methods for implementing a teaching pedagogy that has often been misunderstood or implemented without fidelity, and therefore ineffective. Each quadrant's description and detail provide educators with guidance, supporting their individual musical growth, facilitating authentic relationships with students, authentic performances, and careful idea development for lesson planning that is inclusive of multiple musical perspectives and origins. Muñiz and Richards et al. acknowledged that community support and teacher capacity are essential for culturally relevant pedagogy to be implemented effectively, thus increasing students' academic growth.

Published
2022
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25. Whole exome and genome sequencing in mendelian disorders: a diagnostic and health economic analysis

Author

Ewans, Lisa J., Minoche, Andre E., Schofield, Deborah, Shrestha, Rupendra, Puttick, Clare, Zhu, Ying, Drew, Alexander, Gayevskiy, Velimir, Elakis, George, Walsh, Corrina, Adès, Lesley C., Colley, Alison, Ellaway, Carolyn, Evans, Carey-Anne, Freckmann, Mary-Louise, Goodwin, Linda, Hackett, Anna, Kamien, Benjamin, Kirk, Edwin P., Lipke, Michelle, Mowat, David, Palmer, Elizabeth, Rajagopalan, Sulekha, Ronan, Anne, Sachdev, Rani, Stevenson, William, Turner, Anne, Wilson, Meredith, Worgan, Lisa, Morel-Kopp, Marie-Christine, Field, Michael, Buckley, Michael F., Cowley, Mark J., Dinger, Marcel E., and Roscioli, Tony

Published
2022
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27. Author Correction: Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders

Author

Wang, Tianyun, Hoekzema, Kendra, Vecchio, Davide, Wu, Huidan, Sulovari, Arvis, Coe, Bradley P, Gillentine, Madelyn A, Wilfert, Amy B, Perez-Jurado, Luis A, Kvarnung, Malin, Sleyp, Yoeri, Earl, Rachel K, Rosenfeld, Jill A, Geisheker, Madeleine R, Han, Lin, Du, Bing, Barnett, Chris, Thompson, Elizabeth, Shaw, Marie, Carroll, Renee, Friend, Kathryn, Catford, Rachael, Palmer, Elizabeth E, Zou, Xiaobing, Ou, Jianjun, Li, Honghui, Guo, Hui, Gerdts, Jennifer, Avola, Emanuela, Calabrese, Giuseppe, Elia, Maurizio, Greco, Donatella, Lindstrand, Anna, Nordgren, Ann, Anderlid, Britt-Marie, Vandeweyer, Geert, Van Dijck, Anke, Van der Aa, Nathalie, McKenna, Brooke, Hancarova, Miroslava, Bendova, Sarka, Havlovicova, Marketa, Malerba, Giovanni, Bernardina, Bernardo Dalla, Muglia, Pierandrea, van Haeringen, Arie, Hoffer, Mariette JV, Franke, Barbara, Cappuccio, Gerarda, Delatycki, Martin, Lockhart, Paul J, Manning, Melanie A, Liu, Pengfei, Scheffer, Ingrid E, Brunetti-Pierri, Nicola, Rommelse, Nanda, Amaral, David G, Santen, Gijs WE, Trabetti, Elisabetta, Sedláček, Zdeněk, Michaelson, Jacob J, Pierce, Karen, Courchesne, Eric, Kooy, R Frank, Nordenskjöld, Magnus, Romano, Corrado, Peeters, Hilde, Bernier, Raphael A, Gecz, Jozef, Xia, Kun, and Eichler, Evan E

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Commerce, Management, Tourism and Services, SPARK Consortium
Abstract

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Published
2020

28. Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders

Author

Wang, Tianyun, Hoekzema, Kendra, Vecchio, Davide, Wu, Huidan, Sulovari, Arvis, Coe, Bradley P, Gillentine, Madelyn A, Wilfert, Amy B, Perez-Jurado, Luis A, Kvarnung, Malin, Sleyp, Yoeri, Earl, Rachel K, Rosenfeld, Jill A, Geisheker, Madeleine R, Han, Lin, Du, Bing, Barnett, Chris, Thompson, Elizabeth, Shaw, Marie, Carroll, Renee, Friend, Kathryn, Catford, Rachael, Palmer, Elizabeth E, Zou, Xiaobing, Ou, Jianjun, Li, Honghui, Guo, Hui, Gerdts, Jennifer, Avola, Emanuela, Calabrese, Giuseppe, Elia, Maurizio, Greco, Donatella, Lindstrand, Anna, Nordgren, Ann, Anderlid, Britt-Marie, Vandeweyer, Geert, Van Dijck, Anke, Van der Aa, Nathalie, McKenna, Brooke, Hancarova, Miroslava, Bendova, Sarka, Havlovicova, Marketa, Malerba, Giovanni, Bernardina, Bernardo Dalla, Muglia, Pierandrea, van Haeringen, Arie, Hoffer, Mariette JV, Franke, Barbara, Cappuccio, Gerarda, Delatycki, Martin, Lockhart, Paul J, Manning, Melanie A, Liu, Pengfei, Scheffer, Ingrid E, Brunetti-Pierri, Nicola, Rommelse, Nanda, Amaral, David G, Santen, Gijs WE, Trabetti, Elisabetta, Sedláček, Zdeněk, Michaelson, Jacob J, Pierce, Karen, Courchesne, Eric, Kooy, R Frank, Nordenskjöld, Magnus, Romano, Corrado, Peeters, Hilde, Bernier, Raphael A, Gecz, Jozef, Xia, Kun, and Eichler, Evan E

Subjects
Genetics, Prevention, 2.1 Biological and endogenous factors, Aetiology, Basic Helix-Loop-Helix Transcription Factors, CCCTC-Binding Factor, Case-Control Studies, Cohort Studies, DNA Mutational Analysis, DNA-Binding Proteins, Female, Genetic Association Studies, Genetic Predisposition to Disease, Heterogeneous-Nuclear Ribonucleoprotein U, High-Throughput Nucleotide Sequencing, Humans, KCNQ3 Potassium Channel, Male, Mutation, Neurodevelopmental Disorders, RNA-Binding Proteins, Repressor Proteins, Transcription Factors, SPARK Consortium
Abstract

Most genes associated with neurodevelopmental disorders (NDDs) were identified with an excess of de novo mutations (DNMs) but the significance in case-control mutation burden analysis is unestablished. Here, we sequence 63 genes in 16,294 NDD cases and an additional 62 genes in 6,211 NDD cases. By combining these with published data, we assess a total of 125 genes in over 16,000 NDD cases and compare the mutation burden to nonpsychiatric controls from ExAC. We identify 48 genes (25 newly reported) showing significant burden of ultra-rare (MAF

Published
2020

29. De Novo Variants Disrupting the HX Repeat Motif of ATN1 Cause a Recognizable Non-Progressive Neurocognitive Syndrome

Author

Palmer, Elizabeth E, Hong, Seungbeom, Zahrani, Fatema Al, Hashem, Mais O, Aleisa, Fajr A, Ahmed, Heba M Jalal, Kandula, Tejaswi, Macintosh, Rebecca, Minoche, Andre E, Puttick, Clare, Gayevskiy, Velimir, Drew, Alexander P, Cowley, Mark J, Dinger, Marcel, Rosenfeld, Jill A, Xiao, Rui, Cho, Megan T, Yakubu, Suliat F, Henderson, Lindsay B, Sacoto, Maria J Guillen, Begtrup, Amber, Hamad, Muddathir, Shinawi, Marwan, Andrews, Marisa V, Jones, Marilyn C, Lindstrom, Kristin, Bristol, Ruth E, Kayani, Saima, Snyder, Molly, Villanueva, María Mercedes, Schteinschnaider, Angeles, Faivre, Laurence, Thauvin, Christel, Vitobello, Antonio, Roscioli, Tony, Kirk, Edwin P, Bye, Ann, Merzaban, Jasmeen, Jaremko, Łukasz, Jaremko, Mariusz, Sachdev, Rani K, Alkuraya, Fowzan S, and Arold, Stefan T

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Neurodegenerative, Rare Diseases, Genetics, Pediatric, Brain Disorders, Neurosciences, 2.1 Biological and endogenous factors, Aetiology, Amino Acid Motifs, Child, Child, Preschool, Female, Genetic Variation, Humans, Infant, Male, Nerve Tissue Proteins, Neurocognitive Disorders, Phenotype, Prognosis, Repetitive Sequences, Nucleic Acid, Syndrome, HX repeat, allelic disorders, developmental delay, dysmorphic, intellectual disability, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

Polyglutamine expansions in the transcriptional co-repressor Atrophin-1, encoded by ATN1, cause the neurodegenerative condition dentatorubral-pallidoluysian atrophy (DRPLA) via a proposed novel toxic gain of function. We present detailed phenotypic information on eight unrelated individuals who have de novo missense and insertion variants within a conserved 16-amino-acid "HX repeat" motif of ATN1. Each of the affected individuals has severe cognitive impairment and hypotonia, a recognizable facial gestalt, and variable congenital anomalies. However, they lack the progressive symptoms typical of DRPLA neurodegeneration. To distinguish this subset of affected individuals from the DRPLA diagnosis, we suggest using the term CHEDDA (congenital hypotonia, epilepsy, developmental delay, digit abnormalities) to classify the condition. CHEDDA-related variants alter the particular structural features of the HX repeat motif, suggesting that CHEDDA results from perturbation of the structural and functional integrity of the HX repeat. We found several non-homologous human genes containing similar motifs of eight to 10 HX repeat sequences, including RERE, where disruptive variants in this motif have also been linked to a separate condition that causes neurocognitive and congenital anomalies. These findings suggest that perturbation of the HX motif might explain other Mendelian human conditions.

Published
2019

35. Integrated Care for People Living With Rare Disease: A Scoping Review on Primary Care Models in Organization for Economic Cooperation and Development Countries.

Author

Vidic, Nada, McGlynn, Anna, Abdi, Fatemeh, Tam, Chun Wah Michael, Crampton, Reginald Michael, Lim, Kean-Seng, Palmer, Elizabeth Emma, Taylor, Natalie, and Harris-Roxas, Ben

Subjects
HEALTH services accessibility, GREY literature, PRIMARY health care, RARE diseases, EVALUATION of medical care, PATIENT care, CONTINUUM of care, DESCRIPTIVE statistics, SYSTEMATIC reviews, QUALITY assurance, INTEGRATED health care delivery, MEDICAL care costs
Abstract

Introduction/Objectives: Individually rare, rare diseases are collectively common resulting in frequent health system use. Navigating the health system persists as a challenge. Primary care provides longitudinal contact with the health system and is placed to provide integrated rare-disease-care. Methods: This scoping review used Joanna Briggs Institute and PRISMA methods with a Consolidated Framework for Implementation Research based data extraction tool to find how integrated rare-disease-care is delivered, enablers and barriers to the same, in primary care settings in contemporary literature in OECD countries. Results: The Primary Care Provider (PCP) role varies from routine primary care to shared-rare-disease-care models. In the 26 papers, the most frequently cited PCP roles included involvement in diagnosis (n = 14), care coordination (n = 16), primary and preventative care (n = 18), management of components of rare-disease-care (n = 13), and treatment monitoring (n = 10). Individuals whose PCP was actively involved in their care were reported to have shortened diagnostic delay, improved transitions of care across the lifespan, reduced unplanned utilization of emergency and hospital services, comprehensive psychosocial care, improved quality of life across environments including home, school and work and improved palliative care experiences. Conclusions: Sufficient communication from specialists, information, resources, time and reimbursement for complex care are still needed. Future integrated-rare-disease-care models should be developed by, or with, PCPs. [ABSTRACT FROM AUTHOR]

Published
2025
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36. Psychosocial experiences of clinicians providing care for children with severe neurological impairment.

Author

Nevin, Suzanne M., Le Marne, Fleur A., Beavis, Erin, Macintosh, Rebecca, Palmer, Elizabeth E., Sachdev, Rani, Nunn, Kenneth, Bye, Ann, van Beek, Anna, Wittekind, Carola, Shalhoub, Carolyn, Lau, Christine Yuen‐Yan, Elliot, Christopher, Rogers, David, Wijetilaka, Devika, Argent, Elizabeth, Cotterell, Elizabeth, Jacobson, Erica Elizabeth, McCarthy, Hugh, and Sampaio, Hugo

Subjects
CHILD care, THEMATIC analysis, PSYCHOLOGICAL factors, CHILDREN with epilepsy, PSYCHOEDUCATION
Abstract

Aim: To investigate clinicians' psychosocial experiences navigating interdisciplinary care for children with severe neurological impairment (SNI), for example children with a developmental epileptic encephalopathy; secondarily, to identify preferences for future interventions to support clinicians caring for children with SNI. Method: We conducted a qualitative descriptive study with interdisciplinary clinicians by using a purposeful sampling recruitment strategy. Twenty‐four participants with expertise caring for children with SNI completed in‐depth, semi‐structured interviews. We transcribed the interviews, de‐identified them, and performed inductive thematic analysis. Results: Thematic analysis elicited interrelated themes. Clinicians experienced immense professional barriers providing patient‐centred care across fragmented healthcare contexts. Physical, emotional, and psychological impacts were attributed to inadequate reflective practice training and a paucity of integrated resources to support clinicians over time. Multipronged strategies were prioritized by clinicians, incorporating psychoeducation, interdisciplinary peer mentorship, and psychological resources to build reflective practice skills for clinicians providing complex care in an advancing era of medicine. Interpretation: This study provides novel and in‐depth insight into clinicians' experiences navigating care for children with SNI. The results will be used to inform future integrated and multipronged co‐developed resources tailored for clinicians, on the basis of their recommendations. [ABSTRACT FROM AUTHOR]

Published
2024
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40. Standardized practices for RNA diagnostics using clinically accessible specimens reclassifies 75% of putative splicing variants

Author

Abdulrasool, Ghusoon, Akesson, Lauren S., Al Eryani, Ghamdan, Al-Shinnag, Mohammad, Arts, Peer, Bagnall, Richard, Baker, Naomi L., Barnett, Christopher, Beecroft, Sarah, Bennetts, Bruce, Berbic, Marina, Beshay, Victoria, Black, Michael, Blackburn, Jim, Blombery, Piers, Boggs, Kirsten, Bournazos, Adam M., Branford, Susan, Breen, Jimmy, Brown, Natasha J., Bryen, Samantha J., Burnett, Leslie, Canson, Daffodil, Cheong, Pak, Chew, Edward, Chong, Belinda, Christodoulou, John, Chung, Seo-Kyung, Clark, Mike, Cliffe, Corrina, Cole, Melissa, Collins, Felicity, Compton, Alison, Cooper, Antony, Cooper, Sandra T., Corbett, Mark, Cowley, Mark, Davis, Mark R., Delatycki, Martin, Dudding, Tracy, Edwards, Matthew, Eggers, Stefanie, Ewans, Lisa J., Eyras, Eduardo, Faiz, Fathimath, Fernandez, Miriam Fanjul, Fellowes, Andrew, Fennell, Andrew, Field, Michael, Fleischer, Ron, Folland, Chiara, Fox, Lucy, Freckmann, Mary-Louise, Gaff, Clara, Galea, Melanie, Ghaoui, Roula, Goel, Himanshu, Gornanitis, Ilias, Ha, Thuong, Hanna, Bernadette, Harraway, James, Hayashi, Rippei, Hayes, Ian, Henderson, Alex, Hesson, Luke, Heyer, Erin, Hildebrand, Michael, Hipwell, Michael, Ho, Gladys, Horton, Ari E., Hoskins, Cass, Hunter, Matthew F., Jackson, Matilda, James, Paul, Jones, Kristi J., Wong, Justin Jong-Leong, Josephi-Taylor, Sarah, Joshi, Himanshu, Kassahn, Karin, Kaub, Peter, Kevin, Lucy, Kirk, Edwin, Krzesinski, Emma, Kumble, Smitha, Kummerfeld, Sarah, Laing, Nigel, Lau, Chiyan, Lee, Eric, Leighton, Sarah, Lundie, Ben, Lunke, Sebastian, Mallawaarachchi, Amali, Mayoh, Chelsea, McGaughran, Julie, McLean, Alison, McPhillips, Mary, Meldrum, Cliff, Middleton, Edwina, Milnes, Di, Mina, Kym, Mowat, David, Nisselle, Amy, Oates, Emily, Oshlack, Alicia, Palmer, Elizabeth E., Parasivam, Gayathri, Parsons, Michael, Patel, Chirag, Pinner, Jason R., Quinn, Michael, Rasko, John, Ravenscroft, Gina, Ravine, Anja, Recsei, Krista, Regan, Matthew, Rehn, Jacqueline, Riley, Lisa G., Robertson, Stephen, Ronan, Anne, Roscioli, Tony, Ryland, Georgina, Sadedin, Simon, Sandaradura, Sarah A., Schreiber, Andreas, Scott, Hamish, Scott, Rodney, Semsarian, Christopher, Simons, Cas, Singer, Emma, Smith, Janine M., Smyth, Renee, Spurdle, Amanda, Stark, Zornitza, Sullivan, Patricia, Sundercombe, Samantha, Tan, Tiong Y., Tchan, Michel C., Thompson, Bryony A., Thorburn, David, Toubia, John, Trent, Ronald, Tudini, Emma, Voneague, Irina, Waddell, Leigh, Walker, Logan, Wallis, Mathew, Warnock, Nick, Weatheritt, Robert, White, Deborah, White, Susan M., Williams, Mark G., Wilson, Meredith J., Winship, Ingrid, Worgan, Lisa, Wright, Dale C., Wu, Kathy, Yeung, Alison, Ziolowski, Andrew, Bommireddipalli, Shobhana, Ades, Lesley, Alexander, Stephen I., Archibald, Alison D., Balasubramaniam, Shanti, Berman, Yemima, Bojadzieva, Jasmina, Buckley, Michael F., Dawes, Ruebena, Donaldson, Liz, Downie, Lilian, Edwards, Caitlin, Engel, Amanda, Gallacher, Lyndon, Gear, Russell, Goh, Shuxiang, Goodwin, Linda, Higgins, Megan, Hopper, Bruce K., Huq, Aamira J., Kumar, Kishore R., Lemckert, Frances, Leventer, Richard J., Lindsey-Temple, Suzanna E., Ma, Alan, Macaskill, Steven, Marty, Melanie, Marum, Justine E., McCarthy, Hugh J., Menezes, Manoj P., Mohammad, Shekeeb, Niaz, Aram, Patel, Shilpan G., Phelan, Dean, Rajagopalan, Sulekha, Rodgers, Jonathan, Rodrigues, Miriam, Roxburgh, Richard H., Sachdev, Rani, Samarasekera, Ruvishani, Savva, Elena, Schindler, Tim, Shah, Margit, Sinnerbrink, Ingrid B., Smith, Richard J., Springer, Amanda, Strom, Samuel P., Sue, Carolyn M., Tan, Kenneth, Tantsis, Esther, Trainer, Alison H., van Spaendonck-Zwarts, Karin, Walsh, Rebecca, Warwick, Linda, White, Stephanie, Wong, Wui Kwan, Yap, Patrick, and Young, Helen

Published
2022
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46. PIGG variant pathogenicity assessment reveals characteristic features within 19 families

Author

Tremblay-Laganière, Camille, Maroofian, Reza, Nguyen, Thi Tuyet Mai, Karimiani, Ehsan Ghayoor, Kirmani, Salman, Akbar, Fizza, Ibrahim, Shahnaz, Afroze, Bushra, Doosti, Mohammad, Ashrafzadeh, Farah, Babaei, Meisam, Efthymiou, Stephanie, Christoforou, Marilena, Sultan, Tipu, Ladda, Roger L., McLaughlin, Heather M., Truty, Rebecca, Mahida, Sonal, Cohen, Julie S., Baranano, Kristin, Ismail, Fatima Y., Patel, Millan S., Lehman, Anna, Edmondson, Andrew C., Nagy, Amanda, Walker, Melissa A., Mercimek-Andrews, Saadet, Maki, Yuta, Sachdev, Rani, Macintosh, Rebecca, Palmer, Elizabeth E., Mancini, Grazia M.S., Barakat, Tahsin Stefan, Steinfeld, Robert, Rüsch, Christina T., Stettner, Georg M., Wagner, Matias, Wortmann, Saskia B., Kini, Usha, Brady, Angela F., Stals, Karen L., Ismayilova, Naila, Ellard, Sian, Bernardo, Danilo, Nugent, Kimberly, McLean, Scott D., Antonarakis, Stylianos E., Houlden, Henry, Kinoshita, Taroh, Campeau, Philippe M., and Murakami, Yoshiko

Published
2021
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50. DNM1 encephalopathy

Author

von Spiczak, Sarah, Helbig, Katherine L, Shinde, Deepali N, Huether, Robert, Pendziwiat, Manuela, Lourenço, Charles, Nunes, Mark E, Sarco, Dean P, Kaplan, Richard A, Dlugos, Dennis J, Kirsch, Heidi, Slavotinek, Anne, Cilio, Maria R, Cervenka, Mackenzie C, Cohen, Julie S, McClellan, Rebecca, Fatemi, Ali, Yuen, Amy, Sagawa, Yoshimi, Littlejohn, Rebecca, McLean, Scott D, Hernandez-Hernandez, Laura, Maher, Bridget, Møller, Rikke S, Palmer, Elizabeth, Lawson, John A, Campbell, Colleen A, Joshi, Charuta N, Kolbe, Diana L, Hollingsworth, Georgie, Neubauer, Bernd A, Muhle, Hiltrud, Stephani, Ulrich, Scheffer, Ingrid E, Pena, Sérgio DJ, Sisodiya, Sanjay M, and Helbig, Ingo

Subjects
Neurosciences, Intellectual and Developmental Disabilities (IDD), Genetics, Clinical Research, Brain Disorders, Epilepsy, Pediatric, Neurodegenerative, Aetiology, 2.1 Biological and endogenous factors, Adolescent, Brain Diseases, Child, Child, Preschool, Cohort Studies, DNA Mutational Analysis, Dynamins, Female, GTP Phosphohydrolases, Homeodomain Proteins, Humans, Infant, Male, Microtubule-Associated Proteins, Mitochondrial Proteins, Models, Molecular, Mutation, Phenotype, Short Stature Homeobox Protein, Siblings, Synaptic Vesicles, Young Adult, Epi4K Consortium, EuroEPINOMICS-RES NLES Working Group, Clinical Sciences, Cognitive Sciences, Neurology & Neurosurgery
Abstract

ObjectiveTo evaluate the phenotypic spectrum caused by mutations in dynamin 1 (DNM1), encoding the presynaptic protein DNM1, and to investigate possible genotype-phenotype correlations and predicted functional consequences based on structural modeling.MethodsWe reviewed phenotypic data of 21 patients (7 previously published) with DNM1 mutations. We compared mutation data to known functional data and undertook biomolecular modeling to assess the effect of the mutations on protein function.ResultsWe identified 19 patients with de novo mutations in DNM1 and a sibling pair who had an inherited mutation from a mosaic parent. Seven patients (33.3%) carried the recurrent p.Arg237Trp mutation. A common phenotype emerged that included severe to profound intellectual disability and muscular hypotonia in all patients and an epilepsy characterized by infantile spasms in 16 of 21 patients, frequently evolving into Lennox-Gastaut syndrome. Two patients had profound global developmental delay without seizures. In addition, we describe a single patient with normal development before the onset of a catastrophic epilepsy, consistent with febrile infection-related epilepsy syndrome at 4 years. All mutations cluster within the GTPase or middle domains, and structural modeling and existing functional data suggest a dominant-negative effect on DMN1 function.ConclusionsThe phenotypic spectrum of DNM1-related encephalopathy is relatively homogeneous, in contrast to many other genetic epilepsies. Up to one-third of patients carry the recurrent p.Arg237Trp variant, which is now one of the most common recurrent variants in epileptic encephalopathies identified to date. Given the predicted dominant-negative mechanism of this mutation, this variant presents a prime target for therapeutic intervention.

Published
2017

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