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30 results on '"Kozenko, Mariya"'

1. Assessing the quality and value of metabolic chart data for capturing core outcomes for pediatric medium-chain acyl-CoA dehydrogenase (MCAD) deficiency

Author

Iverson, Ryan, Taljaard, Monica, Geraghty, Michael T., Pugliese, Michael, Tingley, Kylie, Coyle, Doug, Kronick, Jonathan B., Wilson, Kumanan, Austin, Valerie, Brunel-Guitton, Catherine, Buhas, Daniela, Butcher, Nancy J., Chan, Alicia K. J., Dyack, Sarah, Goobie, Sharan, Greenberg, Cheryl R., Jain-Ghai, Shailly, Inbar-Feigenberg, Michal, Karp, Natalya, Kozenko, Mariya, Langley, Erica, Lines, Matthew, Little, Julian, MacKenzie, Jennifer, Maranda, Bruno, Mercimek-Andrews, Saadet, Mhanni, Aizeddin, Mitchell, John J., Nagy, Laura, Offringa, Martin, Pender, Amy, Potter, Murray, Prasad, Chitra, Ratko, Suzanne, Salvarinova, Ramona, Schulze, Andreas, Siriwardena, Komudi, Sondheimer, Neal, Sparkes, Rebecca, Stockler-Ipsiroglu, Sylvia, Tapscott, Kendra, Trakadis, Yannis, Turner, Lesley, Van Karnebeek, Clara, Vandersteen, Anthony, Walia, Jagdeep S., Wilson, Brenda J., Yu, Andrea C., Potter, Beth K., and Chakraborty, Pranesh

Published
2024
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2. Heterozygous variants in MYH10 associated with neurodevelopmental disorders and congenital anomalies with evidence for primary cilia-dependent defects in Hedgehog signaling.

Author

Holtz, Alexander, VanCoillie, Rachel, Vansickle, Elizabeth, Carere, Deanna, Withrow, Kara, Torti, Erin, Juusola, Jane, Millan, Francisca, Person, Richard, Guillen Sacoto, Maria, Si, Yue, Wentzensen, Ingrid, Pugh, Jada, Vasileiou, Georgia, Rieger, Melissa, Reis, André, Aldinger, Kimberly, Dobyns, William, Brunet, Theresa, Hoefele, Julia, Wagner, Matias, Haber, Benjamin, Kotzaeridou, Urania, Keren, Boris, Heron, Delphine, Mignot, Cyril, Heide, Solveig, Courtin, Thomas, Buratti, Julien, Murugasen, Serini, Donald, Kirsten, OHeir, Emily, Moody, Shade, Kim, Katherine, Burton, Barbara, Yoon, Grace, Campo, Miguel, Masser-Frye, Diane, Kozenko, Mariya, Parkinson, Christina, Sell, Susan, Gordon, Patricia, Prokop, Jeremy, Karaa, Amel, Bupp, Caleb, Raby, Benjamin, Sherr, Elliott, and Argilli, Emanuela

Subjects
Hedgehog signaling, MYH10, Neurodevelopmental disorder, Nonmuscle myosin, Primary cilia, Actins, Cilia, Hedgehog Proteins, Humans, Myosin Heavy Chains, Neurodevelopmental Disorders, Nonmuscle Myosin Type IIB
Abstract

PURPOSE: Nonmuscle myosin II complexes are master regulators of actin dynamics that play essential roles during embryogenesis with vertebrates possessing 3 nonmuscle myosin II heavy chain genes, MYH9, MYH10, and MYH14. As opposed to MYH9 and MYH14, no recognizable disorder has been associated with MYH10. We sought to define the clinical characteristics and molecular mechanism of a novel autosomal dominant disorder related to MYH10. METHODS: An international collaboration identified the patient cohort. CAS9-mediated knockout cell models were used to explore the mechanism of disease pathogenesis. RESULTS: We identified a cohort of 16 individuals with heterozygous MYH10 variants presenting with a broad spectrum of neurodevelopmental disorders and variable congenital anomalies that affect most organ systems and were recapitulated in animal models of altered MYH10 activity. Variants were typically de novo missense changes with clustering observed in the motor domain. MYH10 knockout cells showed defects in primary ciliogenesis and reduced ciliary length with impaired Hedgehog signaling. MYH10 variant overexpression produced a dominant-negative effect on ciliary length. CONCLUSION: These data presented a novel genetic cause of isolated and syndromic neurodevelopmental disorders related to heterozygous variants in the MYH10 gene with implications for disrupted primary cilia length control and altered Hedgehog signaling in disease pathogenesis.

Published
2022

3. Upregulation versus loss of function of NTRK2 in 44 affected individuals leads to 2 distinct neurodevelopmental disorders

Author

Berger, Eva, Jauss, Robin-Tobias, Ranells, Judith D., Zonic, Emir, von Wintzingerode, Lydia, Wilson, Ashley, Wagner, Johannes, Tuttle, Annabelle, Thomas-Wilson, Amanda, Schulte, Björn, Rabin, Rachel, Pappas, John, Odgis, Jacqueline A., Muthaffar, Osama, Mendez-Fadol, Alejandra, Lynch, Matthew, Levy, Jonathan, Lehalle, Daphné, Lake, Nicole J., Krey, Ilona, Kozenko, Mariya, Knierim, Ellen, Jouret, Guillaume, Jobanputra, Vaidehi, Isidor, Bertrand, Hunt, David, Hsieh, Tzung-Chien, Holtz, Alexander M., Haack, Tobias B., Gold, Nina B., Dunstheimer, Désirée, Donge, Mylène, Deb, Wallid, De La Rosa Poueriet, Katlin A., Danyel, Magdalena, Christodoulou, John, Chopra, Saurabh, Callewaert, Bert, Busche, Andreas, Brick, Lauren, Bigay, Bary G., Arlt, Marie, Anikar, Swathi S., Almohammal, Mohammad N., Almanza, Deanna, Alhashem, Amal, Bertoli-Avella, Aida, Sticht, Heinrich, and Jamra, Rami Abou

Published
2024
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4. Bi-allelic Loss of Human APC2, Encoding Adenomatous Polyposis Coli Protein 2, Leads to Lissencephaly, Subcortical Heterotopia, and Global Developmental Delay

Author

Lee, Sangmoon, Chen, Dillon Y, Zaki, Maha S, Maroofian, Reza, Houlden, Henry, Di Donato, Nataliya, Abdin, Dalia, Morsy, Heba, Mirzaa, Ghayda M, Dobyns, William B, McEvoy-Venneri, Jennifer, Stanley, Valentina, James, Kiely N, Mancini, Grazia MS, Schot, Rachel, Kalayci, Tugba, Altunoglu, Umut, Karimiani, Ehsan Ghayoor, Brick, Lauren, Kozenko, Mariya, Jamshidi, Yalda, Manzini, M Chiara, Toosi, Mehran Beiraghi, and Gleeson, Joseph G

Subjects
Biological Sciences, Neurosciences, Intellectual and Developmental Disabilities (IDD), Brain Disorders, Neurological, Alleles, Classical Lissencephalies and Subcortical Band Heterotopias, Cytoskeletal Proteins, Developmental Disabilities, Female, Humans, Lissencephaly, Male, Pedigree, APC2, agyria, band heterotopia, epilepsy, intellectual disability, lissencephaly, neuronal migration, pachygyria, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

Lissencephaly is a severe brain malformation in which failure of neuronal migration results in agyria or pachygyria and in which the brain surface appears unusually smooth. It is often associated with microcephaly, profound intellectual disability, epilepsy, and impaired motor abilities. Twenty-two genes are associated with lissencephaly, accounting for approximately 80% of disease. Here we report on 12 individuals with a unique form of lissencephaly; these individuals come from eight unrelated families and have bi-allelic mutations in APC2, encoding adenomatous polyposis coli protein 2. Brain imaging studies demonstrate extensive posterior predominant lissencephaly, similar to PAFAH1B1-associated lissencephaly, as well as co-occurrence of subcortical heterotopia posterior to the caudate nuclei, "ribbon-like" heterotopia in the posterior frontal region, and dysplastic in-folding of the mesial occipital cortex. The established role of APC2 in integrating the actin and microtubule cytoskeletons to mediate cellular morphological changes suggests shared function with other lissencephaly-encoded cytoskeletal proteins such as α-N-catenin (CTNNA2) and platelet-activating factor acetylhydrolase 1b regulatory subunit 1 (PAFAH1B1, also known as LIS1). Our findings identify APC2 as a radiographically distinguishable recessive form of lissencephaly.

Published
2019

5. De Novo and Inherited Loss-of-Function Variants in TLK2: Clinical and Genotype-Phenotype Evaluation of a Distinct Neurodevelopmental Disorder

Author

Reijnders, Margot RF, Miller, Kerry A, Alvi, Mohsan, Goos, Jacqueline AC, Lees, Melissa M, de Burca, Anna, Henderson, Alex, Kraus, Alison, Mikat, Barbara, de Vries, Bert BA, Isidor, Bertrand, Kerr, Bronwyn, Marcelis, Carlo, Schluth-Bolard, Caroline, Deshpande, Charu, Ruivenkamp, Claudia AL, Wieczorek, Dagmar, Study, The Deciphering Developmental Disorders, Baralle, Diana, Blair, Edward M, Engels, Hartmut, Lüdecke, Hermann-Josef, Eason, Jacqueline, Santen, Gijs WE, Clayton-Smith, Jill, Chandler, Kate, Tatton-Brown, Katrina, Payne, Katelyn, Helbig, Katherine, Radtke, Kelly, Nugent, Kimberly M, Cremer, Kirsten, Strom, Tim M, Bird, Lynne M, Sinnema, Margje, Bitner-Glindzicz, Maria, van Dooren, Marieke F, Alders, Marielle, Koopmans, Marije, Brick, Lauren, Kozenko, Mariya, Harline, Megan L, Klaassens, Merel, Steinraths, Michelle, Cooper, Nicola S, Edery, Patrick, Yap, Patrick, Terhal, Paulien A, van der Spek, Peter J, Lakeman, Phillis, Taylor, Rachel L, Littlejohn, Rebecca O, Pfundt, Rolph, Mercimek-Andrews, Saadet, Stegmann, Alexander PA, Kant, Sarina G, McLean, Scott, Joss, Shelagh, Swagemakers, Sigrid MA, Douzgou, Sofia, Wall, Steven A, Küry, Sébastien, Calpena, Eduardo, Koelling, Nils, McGowan, Simon J, Twigg, Stephen RF, Mathijssen, Irene MJ, Nellaker, Christoffer, Brunner, Han G, and Wilkie, Andrew OM

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Biomedical and Clinical Sciences, Genetics, Biotechnology, Brain Disorders, Human Genome, Neurosciences, Clinical Research, Aetiology, 2.1 Biological and endogenous factors, Adolescent, Adult, Base Sequence, Cell Line, Child, Child, Preschool, Facies, Female, Genetic Association Studies, Humans, Infant, Inheritance Patterns, Loss of Function Mutation, Male, Neurodevelopmental Disorders, Protein Kinases, RNA, Messenger, Translocation, Genetic, Young Adult, Deciphering Developmental Disorders Study, Tousled-like, facial averaging, haploinsufficiency, intellectual disability, kinase, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

Next-generation sequencing is a powerful tool for the discovery of genes related to neurodevelopmental disorders (NDDs). Here, we report the identification of a distinct syndrome due to de novo or inherited heterozygous mutations in Tousled-like kinase 2 (TLK2) in 38 unrelated individuals and two affected mothers, using whole-exome and whole-genome sequencing technologies, matchmaker databases, and international collaborations. Affected individuals had a consistent phenotype, characterized by mild-borderline neurodevelopmental delay (86%), behavioral disorders (68%), severe gastro-intestinal problems (63%), and facial dysmorphism including blepharophimosis (82%), telecanthus (74%), prominent nasal bridge (68%), broad nasal tip (66%), thin vermilion of the upper lip (62%), and upslanting palpebral fissures (55%). Analysis of cell lines from three affected individuals showed that mutations act through a loss-of-function mechanism in at least two case subjects. Genotype-phenotype analysis and comparison of computationally modeled faces showed that phenotypes of these and other individuals with loss-of-function variants significantly overlapped with phenotypes of individuals with other variant types (missense and C-terminal truncating). This suggests that haploinsufficiency of TLK2 is the most likely underlying disease mechanism, leading to a consistent neurodevelopmental phenotype. This work illustrates the power of international data sharing, by the identification of 40 individuals from 26 different centers in 7 different countries, allowing the identification, clinical delineation, and genotype-phenotype evaluation of a distinct NDD caused by mutations in TLK2.

Published
2018

6. Defining the clinical phenotype of Saul–Wilson syndrome

Author

Ferreira, Carlos R., Zein, Wadih M., Huryn, Laryssa A., Merker, Andrea, Berger, Seth I., Wilson, William G., Tiller, George E., Wolfe, Lynne A., Merideth, Melissa, Carvalho, Daniel R., Duker, Angela L., Bratke, Heiko, Haug, Marte Gjøl, Rohena, Luis, Hove, Hanne B., Xia, Zhi-Jie, Ng, Bobby G., Freeze, Hudson H., Gabriel, Melissa, Russi, Alvaro H. Serrano, Brick, Lauren, Kozenko, Mariya, Earl, Dawn L., Tham, Emma, Nishimura, Gen, Phillips, John A., III, Gahl, William A., Hamid, Rizwan, Jackson, Andrew P., Grigelioniene, Giedre, and Bober, Michael B.

Published
2020
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7. Evaluation of DNA Methylation Episignatures for Diagnosis and Phenotype Correlations in 42 Mendelian Neurodevelopmental Disorders

Author

Aref-Eshghi, Erfan, Kerkhof, Jennifer, Pedro, Victor P., Barat-Houari, Mouna, Ruiz-Pallares, Nathalie, Andrau, Jean-Christophe, Lacombe, Didier, Van-Gils, Julien, Fergelot, Patricia, Dubourg, Christèle, Cormier-Daire, Valerie, Rondeau, Sophie, Lecoquierre, François, Saugier-Veber, Pascale, Nicolas, Gaël, Lesca, Gaetan, Chatron, Nicolas, Sanlaville, Damien, Vitobello, Antonio, Faivre, Laurence, Thauvin-Robinet, Christel, Laumonnier, Frederic, Raynaud, Martine, Alders, Mariëlle, Mannens, Marcel, Henneman, Peter, Hennekam, Raoul C., Velasco, Guillaume, Francastel, Claire, Ulveling, Damien, Ciolfi, Andrea, Pizzi, Simone, Tartaglia, Marco, Heide, Solveig, Héron, Delphine, Mignot, Cyril, Keren, Boris, Whalen, Sandra, Afenjar, Alexandra, Bienvenu, Thierry, Campeau, Philippe M., Rousseau, Justine, Levy, Michael A., Brick, Lauren, Kozenko, Mariya, Balci, Tugce B., Siu, Victoria Mok, Stuart, Alan, Kadour, Mike, Masters, Jennifer, Takano, Kyoko, Kleefstra, Tjitske, de Leeuw, Nicole, Field, Michael, Shaw, Marie, Gecz, Jozef, Ainsworth, Peter J., Lin, Hanxin, Rodenhiser, David I., Friez, Michael J., Tedder, Matt, Lee, Jennifer A., DuPont, Barbara R., Stevenson, Roger E., Skinner, Steven A., Schwartz, Charles E., Genevieve, David, and Sadikovic, Bekim

Published
2020
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8. Loss of UGP2 in brain leads to a severe epileptic encephalopathy, emphasizing that bi-allelic isoform-specific start-loss mutations of essential genes can cause genetic diseases

Author

Perenthaler, Elena, Nikoncuk, Anita, Yousefi, Soheil, Berdowski, Woutje M., Alsagob, Maysoon, Capo, Ivan, van der Linde, Herma C., van den Berg, Paul, Jacobs, Edwin H., Putar, Darija, Ghazvini, Mehrnaz, Aronica, Eleonora, van IJcken, Wilfred F. J., de Valk, Walter G., Medici-van den Herik, Evita, van Slegtenhorst, Marjon, Brick, Lauren, Kozenko, Mariya, Kohler, Jennefer N., Bernstein, Jonathan A., Monaghan, Kristin G., Begtrup, Amber, Torene, Rebecca, Al Futaisi, Amna, Al Murshedi, Fathiya, Mani, Renjith, Al Azri, Faisal, Kamsteeg, Erik-Jan, Mojarrad, Majid, Eslahi, Atieh, Khazaei, Zaynab, Darmiyan, Fateme Massinaei, Doosti, Mohammad, Karimiani, Ehsan Ghayoor, Vandrovcova, Jana, Zafar, Faisal, Rana, Nuzhat, Kandaswamy, Krishna K., Hertecant, Jozef, Bauer, Peter, AlMuhaizea, Mohammed A., Salih, Mustafa A., Aldosary, Mazhor, Almass, Rawan, Al-Quait, Laila, Qubbaj, Wafa, Coskun, Serdar, Alahmadi, Khaled O., Hamad, Muddathir H. A., Alwadaee, Salem, Awartani, Khalid, Dababo, Anas M., Almohanna, Futwan, Colak, Dilek, Dehghani, Mohammadreza, Mehrjardi, Mohammad Yahya Vahidi, Gunel, Murat, Ercan-Sencicek, A. Gulhan, Passi, Gouri Rao, Cheema, Huma Arshad, Efthymiou, Stephanie, Houlden, Henry, Bertoli-Avella, Aida M., Brooks, Alice S., Retterer, Kyle, Maroofian, Reza, Kaya, Namik, van Ham, Tjakko J., and Barakat, Tahsin Stefan

Published
2020
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9. A Recurrent De Novo Heterozygous COG4 Substitution Leads to Saul-Wilson Syndrome, Disrupted Vesicular Trafficking, and Altered Proteoglycan Glycosylation

Author

Ferreira, Carlos R., Xia, Zhi-Jie, Clément, Aurélie, Parry, David A., Davids, Mariska, Taylan, Fulya, Sharma, Prashant, Turgeon, Coleman T., Blanco-Sánchez, Bernardo, Ng, Bobby G., Logan, Clare V., Wolfe, Lynne A., Solomon, Benjamin D., Cho, Megan T., Douglas, Ganka, Carvalho, Daniel R., Bratke, Heiko, Haug, Marte Gjøl, Phillips, Jennifer B., Wegner, Jeremy, Tiemeyer, Michael, Aoki, Kazuhiro, Nordgren, Ann, Hammarsjö, Anna, Duker, Angela L., Rohena, Luis, Hove, Hanne Buciek, Ek, Jakob, Adams, David, Tifft, Cynthia J., Onyekweli, Tito, Weixel, Tara, Macnamara, Ellen, Radtke, Kelly, Powis, Zöe, Earl, Dawn, Gabriel, Melissa, Russi, Alvaro H. Serrano, Brick, Lauren, Kozenko, Mariya, Tham, Emma, Raymond, Kimiyo M., Phillips, John A., III, Tiller, George E., Wilson, William G., Hamid, Rizwan, Malicdan, May C.V., Nishimura, Gen, Grigelioniene, Giedre, Jackson, Andrew, Westerfield, Monte, Bober, Michael B., Gahl, William A., and Freeze, Hudson H.

Published
2018
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11. Evaluation of DNA Methylation Episignatures for Diagnosis and Phenotype Correlations in 42 Mendelian Neurodevelopmental Disorders

Author

Aref-Eshghi, Erfan, Kerkhof, Jennifer, Pedro, Victor P., France, Groupe DI, Barat-Houari, Mouna, Ruiz-Pallares, Nathalie, Andrau, Jean-Christophe, Lacombe, Didier, Van-Gils, Julien, Fergelot, Patricia, Dubourg, Christéle, Cormier-Daire, Valerie, Rondeau, Sophie, Lecoquierre, François, Saugier-Veber, Pascale, Nicolas, Gaël, Lesca, Gaetan, Chatron, Nicolas, Sanlaville, Damien, Vitobello, Antonio, Faivre, Laurence, Thauvin-Robinet, Christel, Laumonnier, Frederic, Raynaud, Martine, Alders, Mariëlle, Mannens, Marcel, Henneman, Peter, Hennekam, Raoul C., Velasco, Guillaume, Francastel, Claire, Ulveling, Damien, Ciolfi, Andrea, Pizzi, Simone, Tartaglia, Marco, Heide, Solveig, Héron, Delphine, Mignot, Cyril, Keren, Boris, Whalen, Sandra, Afenjar, Alexandra, Bienvenu, Thierry, Campeau, Philippe M., Rousseau, Justine, Levy, Michael A., Brick, Lauren, Kozenko, Mariya, Balci, Tugce B., Siu, Victoria Mok, Stuart, Alan, Kadour, Mike, Masters, Jennifer, Takano, Kyoko, Kleefstra, Tjitske, de Leeuw, Nicole, Field, Michael, Shaw, Marie, Gecz, Jozef, Ainsworth, Peter J., Lin, Hanxin, Rodenhiser, David I., Friez, Michael J., Tedder, Matt, Lee, Jennifer A., DuPont, Barbara R., Stevenson, Roger E., Skinner, Steven A., Schwartz, Charles E., Genevieve, David, and Sadikovic, Bekim

Published
2021
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12. Erratum: Evaluation of DNA Methylation Episignatures for Diagnosis and Phenotype Correlations in 42 Mendelian Neurodevelopmental Disorders (The American Journal of Human Genetics (2020) 106(3) (356–370), (S0002929720300197), (10.1016/j.ajhg.2020.01.019))

Author

Aref-Eshghi, Erfan, Kerkhof, Jennifer, Pedro, Victor P., France, Groupe D. I., Barat-Houari, Mouna, Ruiz-Pallares, Nathalie, Andrau, Jean-Christophe, Lacombe, Didier, van-Gils, Julien, Fergelot, Patricia, Dubourg, Christéle, Cormier-Daire, Valerie, Rondeau, Sophie, Lecoquierre, François, Saugier-Veber, Pascale, Nicolas, Gaël, Lesca, Gaetan, Chatron, Nicolas, Sanlaville, Damien, Vitobello, Antonio, Faivre, Laurence, Thauvin-Robinet, Christel, Laumonnier, Frederic, Raynaud, Martine, Alders, Mariëlle, Mannens, Marcel, Henneman, Peter, Hennekam, Raoul C., Velasco, Guillaume, Francastel, Claire, Ulveling, Damien, Ciolfi, Andrea, Pizzi, Simone, Tartaglia, Marco, Heide, Solveig, Héron, Delphine, Mignot, Cyril, Keren, Boris, Whalen, Sandra, Afenjar, Alexandra, Bienvenu, Thierry, Campeau, Philippe M., Rousseau, Justine, Levy, Michael A., Brick, Lauren, Kozenko, Mariya, Balci, Tugce B., Siu, Victoria Mok, Stuart, Alan, Kadour, Mike, Masters, Jennifer, Takano, Kyoko, Kleefstra, Tjitske, de Leeuw, Nicole, Field, Michael, Shaw, Marie, Gecz, Jozef, Ainsworth, Peter J., Lin, Hanxin, Rodenhiser, David I., Friez, Michael J., Tedder, Matt, Lee, Jennifer A., DuPont, Barbara R., Stevenson, Roger E., Skinner, Steven A., Schwartz, Charles E., Genevieve, David, Sadikovic, Bekim, Human Genetics, ACS - Pulmonary hypertension & thrombosis, Amsterdam Reproduction & Development (AR&D), Amsterdam Gastroenterology Endocrinology Metabolism, General Paediatrics, and APH - Quality of Care

Abstract

(The American Journal of Human Genetics 106, 356–370; March 5, 2020) In the version of this paper originally published, the underlying cause for Hunter McAlpine syndrome was incorrectly described in Table 1. The relevant description has been changed to read “Chr5q35-qter duplication involving NSD1” in the updated Table 1 reflected here. The authors apologize for this error.

Published
2021

16. Heterozygous variants in MYH10associated with neurodevelopmental disorders and congenital anomalies with evidence for primary cilia-dependent defects in Hedgehog signaling

Author

Holtz, Alexander M., VanCoillie, Rachel, Vansickle, Elizabeth A., Carere, Deanna Alexis, Withrow, Kara, Torti, Erin, Juusola, Jane, Millan, Francisca, Person, Richard, Guillen Sacoto, Maria J., Si, Yue, Wentzensen, Ingrid M., Pugh, Jada, Vasileiou, Georgia, Rieger, Melissa, Reis, André, Argilli, Emanuela, Sherr, Elliott H., Aldinger, Kimberly A., Dobyns, William B., Brunet, Theresa, Hoefele, Julia, Wagner, Matias, Haber, Benjamin, Kotzaeridou, Urania, Keren, Boris, Heron, Delphine, Mignot, Cyril, Heide, Solveig, Courtin, Thomas, Buratti, Julien, Murugasen, Serini, Donald, Kirsten A., O’Heir, Emily, Moody, Shade, Kim, Katherine H., Burton, Barbara K., Yoon, Grace, Campo, Miguel del, Masser-Frye, Diane, Kozenko, Mariya, Parkinson, Christina, Sell, Susan L., Gordon, Patricia L., Prokop, Jeremy W., Karaa, Amel, Bupp, Caleb, and Raby, Benjamin A.

Abstract

Nonmuscle myosin II complexes are master regulators of actin dynamics that play essential roles during embryogenesis with vertebrates possessing 3 nonmuscle myosin II heavy chain genes, MYH9, MYH10, and MYH14. As opposed to MYH9and MYH14, no recognizable disorder has been associated with MYH10. We sought to define the clinical characteristics and molecular mechanism of a novel autosomal dominant disorder related to MYH10.

Published
2022
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17. De Novo and Inherited Loss-of-Function Variants in TLK2: Clinical and Genotype-Phenotype Evaluation of a Distinct Neurodevelopmental Disorder

Author

Reijnders, Margot R.F., Miller, Kerry A., Alvi, Mohsan, Goos, Jacqueline A.C., Lees, Melissa M., de Burca, Anna, Henderson, Alex, Kraus, Alison, Mikat, Barbara, de Vries, Bert B.A., Isidor, Bertrand, Kerr, Bronwyn, Marcelis, Carlo, Schluth-Bolard, Caroline, Deshpande, Charu, Ruivenkamp, Claudia A.L., Wieczorek, Dagmar, Baralle, Diana, Blair, Edward M., Engels, Hartmut, Lüdecke, Hermann Josef, Eason, Jacqueline, Santen, Gijs W.E., Clayton-Smith, Jill, Chandler, Kate, Tatton-Brown, Katrina, Payne, Katelyn, Helbig, Katherine, Radtke, Kelly, Nugent, Kimberly M., Cremer, Kirsten, Strom, Tim M., Bird, Lynne M., Sinnema, Margje, Bitner-Glindzicz, Maria, van Dooren, Marieke F., Alders, Marielle, Koopmans, Marije, Brick, Lauren, Kozenko, Mariya, Harline, Megan L., Klaassens, Merel, Steinraths, Michelle, Cooper, Nicola S., Edery, Patrick, Yap, Patrick, Terhal, Paulien A., van der Spek, Peter J., Lakeman, Phillis, Taylor, Rachel L., The Deciphering Developmental Disorders Study, MUMC+: DA KG Polikliniek (9), Kindergeneeskunde, MUMC+: MA Medische Staf Kindergeneeskunde (9), MUMC+: DA KG Lab Centraal Lab (9), RS: GROW - R4 - Reproductive and Perinatal Medicine, Klinische Genetica, and MUMC+: DA Klinische Genetica (5)

Subjects
Male, RNA, Messenger/genetics, Adult, GENES, Adolescent, kinase, Protein Kinases/genetics, Neurodevelopmental Disorders/genetics, Translocation, Genetic, Cell Line, Loss of Function Mutation/genetics, Young Adult, Genetics, Humans, Genetics(clinical), Child, Genetic Association Studies, Tousled-like, Base Sequence, TOUSLED-LIKE KINASES, MUTATIONS, Infant, Facies, haploinsufficiency, Inheritance Patterns/genetics, intellectual disability, Child, Preschool, Female, facial averaging
Abstract

Next-generation sequencing is a powerful tool for the discovery of genes related to neurodevelopmental disorders (NDDs). Here, we report the identification of a distinct syndrome due to de novo or inherited heterozygous mutations in Tousled-like kinase 2 (TLK2) in 38 unrelated individuals and two affected mothers, using whole-exome and whole-genome sequencing technologies, matchmaker databases, and international collaborations. Affected individuals had a consistent phenotype, characterized by mild-borderline neurodevelopmental delay (86%), behavioral disorders (68%), severe gastro-intestinal problems (63%), and facial dysmorphism including blepharophimosis (82%), telecanthus (74%), prominent nasal bridge (68%), broad nasal tip (66%), thin vermilion of the upper lip (62%), and upslanting palpebral fissures (55%). Analysis of cell lines from three affected individuals showed that mutations act through a loss-of-function mechanism in at least two case subjects. Genotype-phenotype analysis and comparison of computationally modeled faces showed that phenotypes of these and other individuals with loss-of-function variants significantly overlapped with phenotypes of individuals with other variant types (missense and C-terminal truncating). This suggests that haploinsufficiency of TLK2 is the most likely underlying disease mechanism, leading to a consistent neurodevelopmental phenotype. This work illustrates the power of international data sharing, by the identification of 40 individuals from 26 different centers in 7 different countries, allowing the identification, clinical delineation, and genotype-phenotype evaluation of a distinct NDD caused by mutations in TLK2.

Published
2018

18. Loss of UGP2 in brain leads to a severe epileptic encephalopathy, emphasizing that bi-allelic isoform-specific start-loss mutations of essential genes can cause genetic diseases

Author

Perenthaler, Elena, primary, Nikoncuk, Anita, additional, Yousefi, Soheil, additional, Berdowski, Woutje M., additional, Alsagob, Maysoon, additional, Capo, Ivan, additional, van der Linde, Herma C., additional, van den Berg, Paul, additional, Jacobs, Edwin H., additional, Putar, Darija, additional, Ghazvini, Mehrnaz, additional, Aronica, Eleonora, additional, van IJcken, Wilfred F. J., additional, de Valk, Walter G., additional, Medici-van den Herik, Evita, additional, van Slegtenhorst, Marjon, additional, Brick, Lauren, additional, Kozenko, Mariya, additional, Kohler, Jennefer N., additional, Bernstein, Jonathan A., additional, Monaghan, Kristin G., additional, Begtrup, Amber, additional, Torene, Rebecca, additional, Al Futaisi, Amna, additional, Al Murshedi, Fathiya, additional, Mani, Renjith, additional, Al Azri, Faisal, additional, Kamsteeg, Erik-Jan, additional, Mojarrad, Majid, additional, Eslahi, Atieh, additional, Khazaei, Zaynab, additional, Darmiyan, Fateme Massinaei, additional, Doosti, Mohammad, additional, Karimiani, Ehsan Ghayoor, additional, Vandrovcova, Jana, additional, Zafar, Faisal, additional, Rana, Nuzhat, additional, Kandaswamy, Krishna K., additional, Hertecant, Jozef, additional, Bauer, Peter, additional, AlMuhaizea, Mohammed A., additional, Salih, Mustafa A., additional, Aldosary, Mazhor, additional, Almass, Rawan, additional, Al-Quait, Laila, additional, Qubbaj, Wafa, additional, Coskun, Serdar, additional, Alahmadi, Khaled O., additional, Hamad, Muddathir H. A., additional, Alwadaee, Salem, additional, Awartani, Khalid, additional, Dababo, Anas M., additional, Almohanna, Futwan, additional, Colak, Dilek, additional, Dehghani, Mohammadreza, additional, Mehrjardi, Mohammad Yahya Vahidi, additional, Gunel, Murat, additional, Ercan-Sencicek, A. Gulhan, additional, Passi, Gouri Rao, additional, Cheema, Huma Arshad, additional, Efthymiou, Stephanie, additional, Houlden, Henry, additional, Bertoli-Avella, Aida M., additional, Brooks, Alice S., additional, Retterer, Kyle, additional, Maroofian, Reza, additional, Kaya, Namik, additional, van Ham, Tjakko J., additional, and Barakat, Tahsin Stefan, additional

Published
2019
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21. De novo mutations in the GTP/GDP-binding region of RALA, a RAS-like small GTPase, cause intellectual disability and developmental delay

Author

Hiatt, Susan M., primary, Neu, Matthew B., additional, Ramaker, Ryne C., additional, Hardigan, Andrew A., additional, Prokop, Jeremy W., additional, Hancarova, Miroslava, additional, Prchalova, Darina, additional, Havlovicova, Marketa, additional, Prchal, Jan, additional, Stranecky, Viktor, additional, Yim, Dwight K. C., additional, Powis, Zöe, additional, Keren, Boris, additional, Nava, Caroline, additional, Mignot, Cyril, additional, Rio, Marlene, additional, Revah-Politi, Anya, additional, Hemati, Parisa, additional, Stong, Nicholas, additional, Iglesias, Alejandro D., additional, Suchy, Sharon F., additional, Willaert, Rebecca, additional, Wentzensen, Ingrid M., additional, Wheeler, Patricia G., additional, Brick, Lauren, additional, Kozenko, Mariya, additional, Hurst, Anna C. E., additional, Wheless, James W., additional, Lacassie, Yves, additional, Myers, Richard M., additional, Barsh, Gregory S., additional, Sedlacek, Zdenek, additional, and Cooper, Gregory M., additional

Published
2018
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22. De novomutations in the GTP/GDP-binding region of RALA, a RAS-like small GTPase, cause intellectual disability and developmental delay

Author

Hiatt, Susan M., primary, Neu, Matthew B., additional, Ramaker, Ryne C., additional, Hardigan, Andrew A., additional, Prokop, Jeremy W., additional, Hancarova, Miroslava, additional, Prchalova, Darina, additional, Havlovicova, Marketa, additional, Prchal, Jan, additional, Stranecky, Viktor, additional, Yim, Dwight K.C., additional, Powis, Zöe, additional, Keren, Boris, additional, Nava, Caroline, additional, Mignot, Cyril, additional, Rio, Marlene, additional, Revah-Politi, Anya, additional, Hemati, Parisa, additional, Stong, Nicholas, additional, Iglesias, Alejandro D., additional, Suchy, Sharon F., additional, Willaert, Rebecca, additional, Wentzensen, Ingrid M., additional, Wheeler, Patricia G., additional, Brick, Lauren, additional, Kozenko, Mariya, additional, Hurst, Anna C.E., additional, Wheless, James W., additional, Lacassie, Yves, additional, Myers, Richard M., additional, Barsh, Gregory S., additional, Sedlacek, Zdenek, additional, and Cooper, Gregory M., additional

Published
2018
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23. De Novo and Inherited Loss-of-Function Variants in TLK2: Clinical and Genotype-Phenotype Evaluation of a Distinct Neurodevelopmental Disorder

Author

Genetica, Genetica Klinische Genetica, Child Health, Reijnders, Margot R.F., Miller, Kerry A., Alvi, Mohsan, Goos, Jacqueline A.C., Lees, Melissa M., de Burca, Anna, Henderson, Alex, Kraus, Alison, Mikat, Barbara, de Vries, Bert B.A., Isidor, Bertrand, Kerr, Bronwyn, Marcelis, Carlo, Schluth-Bolard, Caroline, Deshpande, Charu, Ruivenkamp, Claudia A.L., Wieczorek, Dagmar, Baralle, Diana, Blair, Edward M., Engels, Hartmut, Lüdecke, Hermann Josef, Eason, Jacqueline, Santen, Gijs W.E., Clayton-Smith, Jill, Chandler, Kate, Tatton-Brown, Katrina, Payne, Katelyn, Helbig, Katherine, Radtke, Kelly, Nugent, Kimberly M., Cremer, Kirsten, Strom, Tim M., Bird, Lynne M., Sinnema, Margje, Bitner-Glindzicz, Maria, van Dooren, Marieke F., Alders, Marielle, Koopmans, Marije, Brick, Lauren, Kozenko, Mariya, Harline, Megan L., Klaassens, Merel, Steinraths, Michelle, Cooper, Nicola S., Edery, Patrick, Yap, Patrick, Terhal, Paulien A., van der Spek, Peter J., Lakeman, Phillis, Taylor, Rachel L., The Deciphering Developmental Disorders Study, Genetica, Genetica Klinische Genetica, Child Health, Reijnders, Margot R.F., Miller, Kerry A., Alvi, Mohsan, Goos, Jacqueline A.C., Lees, Melissa M., de Burca, Anna, Henderson, Alex, Kraus, Alison, Mikat, Barbara, de Vries, Bert B.A., Isidor, Bertrand, Kerr, Bronwyn, Marcelis, Carlo, Schluth-Bolard, Caroline, Deshpande, Charu, Ruivenkamp, Claudia A.L., Wieczorek, Dagmar, Baralle, Diana, Blair, Edward M., Engels, Hartmut, Lüdecke, Hermann Josef, Eason, Jacqueline, Santen, Gijs W.E., Clayton-Smith, Jill, Chandler, Kate, Tatton-Brown, Katrina, Payne, Katelyn, Helbig, Katherine, Radtke, Kelly, Nugent, Kimberly M., Cremer, Kirsten, Strom, Tim M., Bird, Lynne M., Sinnema, Margje, Bitner-Glindzicz, Maria, van Dooren, Marieke F., Alders, Marielle, Koopmans, Marije, Brick, Lauren, Kozenko, Mariya, Harline, Megan L., Klaassens, Merel, Steinraths, Michelle, Cooper, Nicola S., Edery, Patrick, Yap, Patrick, Terhal, Paulien A., van der Spek, Peter J., Lakeman, Phillis, Taylor, Rachel L., and The Deciphering Developmental Disorders Study

Published
2018

25. Upregulation vs. loss of function of NTRK2 in 44 affected individuals leads to two distinct neurodevelopmental disorders

Author

Berger, Eva, Jauss, Robin-Tobias, Ranells, Judith D., Zonic, Emir, von Wintzingerode, Lydia, Wilson, Ashley, Wagner, Johannes, Tuttle, Annabelle, Thomas-Wilson, Amanda, Schulte, Björn, Rabin, Rachel, Pappas, John, Odgis, Jacqueline A., Muthaffar, Osama, Mendez-Fadol, Alejandra, Lynch, Matthew, Levy, Jonathan, Lehalle, Daphné, Lake, Nicole J., Krey, Ilona, Kozenko, Mariya, Knierim, Ellen, Jouret, Guillaume, Jobanputra, Vaidehi, Isidor, Bertrand, Hunt, David, Hsieh, Tzung-Chien, Holtz, Alexander M., Haack, Tobias B., Gold, Nina B., Dunstheimer, Désirée, Donge, Mylène, Deb, Wallid, De La Rosa Poueriet, Katlin A., Danyel, Magdalena, Christodoulou, John, Chopra, Saurabh, Callewaert, Bert, Busche, Andreas, Brick, Lauren, Bigay, Bary G., Arlt, Marie, Anikar, Swathi S., Almohammal, Mohammad N., Almanza, Deanna, Alhashem, Amal, Bertoli-Avella, Aida, Sticht, Heinrich, and Jamra, Rami Abou

Abstract

Heterozygous pathogenic variants in NTRK2(HGNC: 8032) have been associated with global developmental delay. However, only scattered cases have been described in small or general studies. The aim of our work was to consolidate our understanding of NTRK2-related disorders and to delineate the clinical presentation

Published
2024
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27. Expanding the Phenotype: Neurodevelopmental Disorder, Mitochondrial, With Abnormal Movements and Lactic Acidosis, With or Without Seizures (NEMMLAS) Due to WARS2 Biallelic Variants, Encoding Mitochondrial Tryptophanyl-tRNA Synthase.

Author

Tarnopolsky, Mark, Kozenko, Mariya, and Jones, Kevin

Subjects
*MELAS syndrome, *LACTIC acidosis, *SEIZURES (Medicine), *DISEASES, *INBORN errors of metabolism, *MITOCHONDRIAL pathology
Abstract

Keywords: developmental delay; genetics; inborn errors of metabolism; mitochondrial disorder; mutation However, given that the c.938A>T variant has already been reported I in trans i with the c.797del mutation in affected siblings confirmed to harbor biallelic I WARS2 i mutations[1], we assumed the c.938A>T was likely inherited by the asymptomatic father; however, we cannot rule out the remote possibility that it arose by spontaneous mutation. [Extracted from the article]

Published
2020
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28. Evaluation of the quality of clinical data collection for a pan-Canadian cohort of children affected by inherited metabolic diseases : lessons learned from the Canadian Inherited Metabolic Diseases Research Network

Author

Tingley, Kylie, Lamoureux, Monica, Pugliese, Michael, Geraghty, Michael T, Kronick, Jonathan B, Potter, Beth K, Coyle, Doug, Wilson, Kumanan, Kowalski, Michael, Austin, Valerie, Brunel-Guitton, Catherine, Buhas, Daniela, Chan, Alicia K J, Dyack, Sarah, Feigenbaum, Annette, Giezen, Alette, Goobie, Sharan, Greenberg, Cheryl R, Ghai, Shailly J, Inbar-Feigenberg, Michal, Karp, Natalya, Kozenko, Mariya, Langley, Erica, Lines, Matthew, Little, Julian, MacKenzie, Jennifer, Maranda, Bruno, Mercimek-Andrews, Saadet, Mohan, Connie, Mhanni, Aizeddin, Mitchell, Grant, Mitchell, John J, Nagy, Laura, Napier, Melanie, Pender, Amy, Potter, Murray, Prasad, Chitra, Ratko, Suzanne, Salvarinova, Ramona, Schulze, Andreas, Siriwardena, Komudi, Sondheimer, Neal, Sparkes, Rebecca, Stockler-Ipsiroglu, Sylvia, Trakadis, Yannis, Turner, Lesley, Van Karnebeek, Clara, Vallance, Hilary, Vandersteen, Anthony, Walia, Jagdeep, Wilson, Ashley, Wilson, Brenda J, Yu, Andrea C, Yuskiv, Nataliya, and Chakraborty, Pranesh

Subjects
3. Good health
Abstract

Background The Canadian Inherited Metabolic Diseases Research Network (CIMDRN) is a pan-Canadian practice-based research network of 14 Hereditary Metabolic Disease Treatment Centres and over 50 investigators. CIMDRN aims to develop evidence to improve health outcomes for children with inherited metabolic diseases (IMD). We describe the development of our clinical data collection platform, discuss our data quality management plan, and present the findings to date from our data quality assessment, highlighting key lessons that can serve as a resource for future clinical research initiatives relating to rare diseases. Methods At participating centres, children born from 2006 to 2015 who were diagnosed with one of 31 targeted IMD were eligible to participate in CIMDRN’s clinical research stream. For all participants, we collected a minimum data set that includes information about demographics and diagnosis. For children with five prioritized IMD, we collected longitudinal data including interventions, clinical outcomes, and indicators of disease management. The data quality management plan included: design of user-friendly and intuitive clinical data collection forms; validation measures at point of data entry, designed to minimize data entry errors; regular communications with each CIMDRN site; and routine review of aggregate data. Results As of June 2019, CIMDRN has enrolled 798 participants of whom 764 (96%) have complete minimum data set information. Results from our data quality assessment revealed that potential data quality issues were related to interpretation of definitions of some variables, participants who transferred care across institutions, and the organization of information within the patient charts (e.g., neuropsychological test results). Little information was missing regarding disease ascertainment and diagnosis (e.g., ascertainment method – 0% missing). Discussion Using several data quality management strategies, we have established a comprehensive clinical database that provides information about care and outcomes for Canadian children affected by IMD. We describe quality issues and lessons for consideration in future clinical research initiatives for rare diseases, including accurately accommodating different clinic workflows and balancing comprehensiveness of data collection with available resources. Integrating data collection within clinical care, leveraging electronic medical records, and implementing core outcome sets will be essential for achieving sustainability.

29. A recurrent de novo HSPD1 variant is associated with hypomyelinating leukodystrophy.

Author

Cömert C, Brick L, Ang D, Palmfeldt J, Meaney BF, Kozenko M, Georgopoulos C, Fernandez-Guerra P, and Bross P

Subjects
Adult, Alleles, Amino Acid Sequence, Amino Acid Substitution, Chaperonin 10 genetics, Chaperonin 60 chemistry, Child, Female, Genotype, Humans, Infant, Magnetic Resonance Imaging, Male, Mitochondrial Proteins chemistry, Models, Molecular, Mutation, Pregnancy Proteins genetics, Protein Conformation, Recurrence, Structure-Activity Relationship, Suppressor Factors, Immunologic genetics, Chaperonin 60 genetics, Genetic Association Studies methods, Genetic Predisposition to Disease, Genetic Variation, Hereditary Central Nervous System Demyelinating Diseases diagnosis, Hereditary Central Nervous System Demyelinating Diseases genetics, Mitochondrial Diseases diagnosis, Mitochondrial Diseases genetics, Mitochondrial Proteins genetics
Abstract

Standardization of the use of next-generation sequencing for the diagnosis of rare neurological disorders has made it possible to detect potential disease-causing genetic variations, including de novo variants. However, the lack of a clear pathogenic relevance of gene variants poses a critical limitation for translating this genetic information into clinical practice, increasing the necessity to perform functional assays. Genetic screening is currently recommended in the guidelines for diagnosis of hypomyelinating leukodystrophies (HLDs). HLDs represent a group of rare heterogeneous disorders that interfere with the myelination of the neurons in the central nervous system. One of the HLD-related genes is HSPD1 , encoding the mitochondrial chaperone heat shock protein 60 (HSP60), which functions as folding machinery for the mitochondrial proteins imported into the mitochondrial matrix space. Disease-causing HSPD1 variants have been associated with an autosomal recessive form of fatal hypomyelinating leukodystrophy (HLD4, MitCHAP60 disease; MIM #612233) and an autosomal dominant form of spastic paraplegia, type 13 (SPG13; MIM #605280). In 2018, a de novo HSPD1 variant was reported in a patient with HLD. Here, we present another case carrying the same heterozygous de novo variation in the HSPD1 gene (c.139T > G, p.Leu47Val) associated with an HLD phenotype. Our molecular studies show that the variant HSP60 protein is stably present in the patient's fibroblasts, and functional assays demonstrate that the variant protein lacks in vivo function, thus confirming its disease association. We conclude that de novo variations of the HSPD1 gene should be considered as potentially disease-causing in the diagnosis and pathogenesis of the HLDs., (© 2020 Cömert et al.; Published by Cold Spring Harbor Laboratory Press.)

Published
2020
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30. Evaluation of the quality of clinical data collection for a pan-Canadian cohort of children affected by inherited metabolic diseases: lessons learned from the Canadian Inherited Metabolic Diseases Research Network.

Author

Tingley K, Lamoureux M, Pugliese M, Geraghty MT, Kronick JB, Potter BK, Coyle D, Wilson K, Kowalski M, Austin V, Brunel-Guitton C, Buhas D, Chan AKJ, Dyack S, Feigenbaum A, Giezen A, Goobie S, Greenberg CR, Ghai SJ, Inbar-Feigenberg M, Karp N, Kozenko M, Langley E, Lines M, Little J, MacKenzie J, Maranda B, Mercimek-Andrews S, Mohan C, Mhanni A, Mitchell G, Mitchell JJ, Nagy L, Napier M, Pender A, Potter M, Prasad C, Ratko S, Salvarinova R, Schulze A, Siriwardena K, Sondheimer N, Sparkes R, Stockler-Ipsiroglu S, Trakadis Y, Turner L, Van Karnebeek C, Vallance H, Vandersteen A, Walia J, Wilson A, Wilson BJ, Yu AC, Yuskiv N, and Chakraborty P

Subjects
Canada, Child, Cohort Studies, Data Collection, Humans, Research Design, Metabolic Diseases
Abstract

Background: The Canadian Inherited Metabolic Diseases Research Network (CIMDRN) is a pan-Canadian practice-based research network of 14 Hereditary Metabolic Disease Treatment Centres and over 50 investigators. CIMDRN aims to develop evidence to improve health outcomes for children with inherited metabolic diseases (IMD). We describe the development of our clinical data collection platform, discuss our data quality management plan, and present the findings to date from our data quality assessment, highlighting key lessons that can serve as a resource for future clinical research initiatives relating to rare diseases., Methods: At participating centres, children born from 2006 to 2015 who were diagnosed with one of 31 targeted IMD were eligible to participate in CIMDRN's clinical research stream. For all participants, we collected a minimum data set that includes information about demographics and diagnosis. For children with five prioritized IMD, we collected longitudinal data including interventions, clinical outcomes, and indicators of disease management. The data quality management plan included: design of user-friendly and intuitive clinical data collection forms; validation measures at point of data entry, designed to minimize data entry errors; regular communications with each CIMDRN site; and routine review of aggregate data., Results: As of June 2019, CIMDRN has enrolled 798 participants of whom 764 (96%) have complete minimum data set information. Results from our data quality assessment revealed that potential data quality issues were related to interpretation of definitions of some variables, participants who transferred care across institutions, and the organization of information within the patient charts (e.g., neuropsychological test results). Little information was missing regarding disease ascertainment and diagnosis (e.g., ascertainment method - 0% missing)., Discussion: Using several data quality management strategies, we have established a comprehensive clinical database that provides information about care and outcomes for Canadian children affected by IMD. We describe quality issues and lessons for consideration in future clinical research initiatives for rare diseases, including accurately accommodating different clinic workflows and balancing comprehensiveness of data collection with available resources. Integrating data collection within clinical care, leveraging electronic medical records, and implementing core outcome sets will be essential for achieving sustainability.

Published
2020
Full Text
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