Clinico-radiological features, molecular spectrum, and identification of prognostic factors in developmental and epileptic encephalopathy due to inosine triphosphate pyrophosphatase (ITPase) deficiency.

Autor: Scala M; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Università Degli Studi di Genova, Genoa, Italy.; Pediatric Neurology and Muscular Diseases Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy.; UCL Queen Square Institute of Neurology, University College London, London, UK., Wortmann SB; Amalia Children's Hospital, Radboud University Nijmegen, Nijmegen, The Netherlands.; University Children's Hospital, Paracelsus Medical University, Salzburg, Austria., Kaya N; Department of Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.; Department of Translational Genomics, Center for Genomics Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia., Stellingwerff MD; Department of Child Neurology, Emma Children's Hospital, Amsterdam Leukodystrophy Center, Amsterdam University Medical Centers, Vrije Universiteit and Amsterdam Neuroscience, Amsterdam, The Netherlands., Pistorio A; Clinical Epidemiology and Biostatistics Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy., Glamuzina E; Adult and Paediatric National Metabolic Service, Starship Children's Hospital, Auckland, New Zealand., van Karnebeek CD; Departments of Pediatrics and Clinical Genetics, Academic Medical Centre, Amsterdam, The Netherlands., Skrypnyk C; Department of Molecular Medicine, Al-Jawhara Centre for Molecular Medicine, Arabian Gulf University, Manama, Kingdom of Bahrain., Iwanicka-Pronicka K; Department of Medical Genetics, The Children's Memorial Health Institute, Warsaw, Poland.; Department of Audiology and Phoniatrics, The Children's Memorial Health Institute, Warsaw, Poland., Piekutowska-Abramczuk D; Department of Medical Genetics, The Children's Memorial Health Institute, Warsaw, Poland., Ciara E; Department of Medical Genetics, The Children's Memorial Health Institute, Warsaw, Poland., Tort F; Secció d'Errors Congènits del Metabolisme-IBC, Servei de Bioquímica iGenètica Molecular, Hospital Clínic, IDIBAPS, CIBERER, Barcelona, Spain., Sheidley B; Department of Neurology, F.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, Massachusettes, USA.; Division of Epilepsy and Clinical Neurophysiology and Epilepsy Genetics Program, Boston Children's Hospital, Boston, Massachusettes, USA., Poduri A; Department of Neurology, F.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, Massachusettes, USA.; Division of Epilepsy and Clinical Neurophysiology and Epilepsy Genetics Program, Boston Children's Hospital, Boston, Massachusettes, USA.; Department of Neurology, Harvard Medical School, Boston, Massachusettes, USA., Jayakar P; Nicklaus Children's Hospital, Miami, Florida, USA., Jayakar A; Nicklaus Children's Hospital, Miami, Florida, USA., Upadia J; Tulane University School of Medicine, New Orleans, Louisiana, USA., Walano N; Tulane University School of Medicine, New Orleans, Louisiana, USA., Haack TB; Institute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany., Prokisch H; Institute of Human Genetics, Technische Universität München, Munich, Germany.; Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany., Aldhalaan H; Department of Neurosciences, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia., Karimiani EG; Department of Medical Genetics, Next Generation Genetic Polyclinic, Mashhad, Iran.; Molecular and Clinical Sciences Institute, St. George's University of London, Cranmer Terrace, London, UK.; Innovative Medical Research Center, Islamic Azad University, Mashhad Branch, Mashhad, Iran., Yildiz Y; Pediatric Metabolic Diseases Clinic, Dr. Sami Ulus Training and Research Hospital for Maternity and Children, Ankara, Turkey., Ceylan AC; Department of Medical Genetics, Ankara City Hospital, Ankara, Turkey., Santiago-Sim T; GeneDx, Gaithersburg, Maryland, USA., Dameron A; GeneDx, Gaithersburg, Maryland, USA., Yang H; GeneDx, Gaithersburg, Maryland, USA., Toosi MB; Pediatric Neurology Department, Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran., Ashrafzadeh F; Department of Pediatrics, Mashhad University of Medical Sciences, Mashhad, Iran., Akhondian J; Pediatric Neurology Department, Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran., Imannezhad S; Department of Pediatric Diseases, Mashhad University of Medical Sciences, Mashhad, Iran., Mirzadeh HS; Department of Pediatric Diseases, Mashhad University of Medical Sciences, Mashhad, Iran., Maqbool S; Development and Behavioral Pediatrics Department, Institute of Child Health and The Children Hospital, Lahore, Pakistan., Farid A; Development and Behavioral Pediatrics Department, Institute of Child Health and The Children Hospital, Lahore, Pakistan., Al-Muhaizea MA; Department of Neurosciences, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia., Alshwameen MO; Department of Neurosciences, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia., Aldowsari L; Department of Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia., Alsagob M; Department of Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia., Alyousef A; Department of Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia., AlMass R; Department of Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia., AlHargan A; Department of Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia., Alwadei AH; Neurosciences Department, King Fahad Medical City, Riyadh, Saudi Arabia., AlRasheed MM; Department of Clinical Pharmacy, King Saud University, Riyadh, Saudi Arabia., Colak D; Department of Biostatistics, Epidemiology and Scientific Computing, KFSHRC, Riyadh, Kingdom of Saudi Arabia., Alqudairy H; Department of Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia., Khan S; Department of Neurosciences, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia., Lines MA; Medical Genetics, Department of Pediatrics, Alberta Children's Hospital, Calgary, Canada., García Cazorla MÁ; Inborn Errors of Metabolism Unit, Hospital Sant Joan de Déu, Barcelona, Spain., Ribes A; Secció d'Errors Congènits del Metabolisme-IBC, Servei de Bioquímica iGenètica Molecular, Hospital Clínic, IDIBAPS, CIBERER, Barcelona, Spain., Morava E; Department of Clinical Genomics, Laboratory of Medicine and Pathology, Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota, USA., Bibi F; Institute of Biochemistry and Biotechnology, Pir Mehar Ali Shah Arid Agriculture University, Rawalpindi, Pakistan., Haider S; Izzat Ali Shah Hospital, Lalarukh Wah Cantt, Rawalpindi, Pakistan., Ferla MP; NIHR Oxford BRC Genomic Medicine, Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK., Taylor JC; NIHR Oxford BRC Genomic Medicine, Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK., Alsaif HS; Department of Translational Genomics, Center for Genomics Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia., Firdous A; Department of Translational Genomics, Center for Genomics Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia., Hashem M; Department of Translational Genomics, Center for Genomics Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia., Shashkin C; International University of Postgraduate Education, Almaty, Kazakhstan., Koneev K; Department of Neurology and Neurosurgery, Asfendiyarov Kazakh National Medical University, Almaty, Kazakhstan., Kaiyrzhanov R; UCL Queen Square Institute of Neurology, University College London, London, UK., Efthymiou S; UCL Queen Square Institute of Neurology, University College London, London, UK., Genomics QS; UCL Queen Square Institute of Neurology, University College London, London, UK., Schmitt-Mechelke T; Department of Neuropaediatrics, Children's Hospital, Cantonal Hospital, Lucerne, Switzerland., Ziegler A; Zentrum für Kinder und Jugendmedizin Heidelberg, Sektion Neuropädiatrie und Stoffwechselmedizin, Universitätsklinikum Heidelberg, Heidelberg, Germany., Issa MY; Clinical Genetics Department, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt., Elbendary HM; Clinical Genetics Department, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt., Striano P; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Università Degli Studi di Genova, Genoa, Italy.; Pediatric Neurology and Muscular Diseases Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy., Alkuraya FS; Department of Translational Genomics, Center for Genomics Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.; Department of Anatomy and Cell Biology, Alfaisal University, Riyadh, Saudi Arabia., Zaki MS; Clinical Genetics Department, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt., Gleeson JG; Department of Neuroscience, Rady Children's Institute for Genomic Medicine, Howard Hughes Medical Institute, University of California, San Diego, California, USA., Barakat TS; Department of Clinical Genetics, Erasmus MC, University Medical Center, Rotterdam, The Netherlands., Bierau J; Laboratory of Biochemical Genetics, Department of Clinical Genetics, Maastricht University Hospital, Maastricht, The Netherlands., van der Knaap MS; Department of Child Neurology, Emma Children's Hospital, Amsterdam Leukodystrophy Center, Amsterdam University Medical Centers, Vrije Universiteit and Amsterdam Neuroscience, Amsterdam, The Netherlands.; Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, VU University, Amsterdam, The Netherlands., Maroofian R; UCL Queen Square Institute of Neurology, University College London, London, UK., Houlden H; UCL Queen Square Institute of Neurology, University College London, London, UK.
Jazyk: angličtina
Zdroj: Human mutation [Hum Mutat] 2022 Mar; Vol. 43 (3), pp. 403-419. Date of Electronic Publication: 2022 Jan 12.
DOI: 10.1002/humu.24326
Abstrakt: Developmental and epileptic encephalopathy 35 (DEE 35) is a severe neurological condition caused by biallelic variants in ITPA, encoding inosine triphosphate pyrophosphatase, an essential enzyme in purine metabolism. We delineate the genotypic and phenotypic spectrum of DEE 35, analyzing possible predictors for adverse clinical outcomes. We investigated a cohort of 28 new patients and reviewed previously described cases, providing a comprehensive characterization of 40 subjects. Exome sequencing was performed to identify underlying ITPA pathogenic variants. Brain MRI (magnetic resonance imaging) scans were systematically analyzed to delineate the neuroradiological spectrum. Survival curves according to the Kaplan-Meier method and log-rank test were used to investigate outcome predictors in different subgroups of patients. We identified 18 distinct ITPA pathogenic variants, including 14 novel variants, and two deletions. All subjects showed profound developmental delay, microcephaly, and refractory epilepsy followed by neurodevelopmental regression. Brain MRI revision revealed a recurrent pattern of delayed myelination and restricted diffusion of early myelinating structures. Congenital microcephaly and cardiac involvement were statistically significant novel clinical predictors of adverse outcomes. We refined the molecular, clinical, and neuroradiological characterization of ITPase deficiency, and identified new clinical predictors which may have a potentially important impact on diagnosis, counseling, and follow-up of affected individuals.
(© 2022 The Authors. Human Mutation published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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