Clinical, neuroimaging, and molecular spectrum of TECPR2-associated hereditary sensory and autonomic neuropathy with intellectual disability.

Adolescent Carrier Proteins / chemistry Child Child, Preschool Cohort Studies Cross-Sectional Studies Family Female Hereditary Sensory and Autonomic Neuropathies / complications Humans Infant Intellectual Disability / complications Magnetic Resonance Imaging Male Models, Molecular Mutation, Missense Nerve Tissue Proteins / chemistry Neuroimaging / methods Pedigree Phenotype Protein Conformation
Human Phenotype Ontology TECPR2 neurodevelopmental disorder sensory autonomic neuropathy spastic paraplegia

Journal

Human mutation
ISSN: 1098-1004
Titre abrégé: Hum Mutat
Pays: United States
ID NLM: 9215429

Informations de publication

Date de publication:
06 2021
Historique:
revised: 18 03 2021
received: 19 10 2020
accepted: 08 04 2021
pubmed: 14 4 2021
medline: 29 1 2022
entrez: 13 4 2021
Statut: ppublish

Résumé

Bi-allelic TECPR2 variants have been associated with a complex syndrome with features of both a neurodevelopmental and neurodegenerative disorder. Here, we provide a comprehensive clinical description and variant interpretation framework for this genetic locus. Through international collaboration, we identified 17 individuals from 15 families with bi-allelic TECPR2-variants. We systemically reviewed clinical and molecular data from this cohort and 11 cases previously reported. Phenotypes were standardized using Human Phenotype Ontology terms. A cross-sectional analysis revealed global developmental delay/intellectual disability, muscular hypotonia, ataxia, hyporeflexia, respiratory infections, and central/nocturnal hypopnea as core manifestations. A review of brain magnetic resonance imaging scans demonstrated a thin corpus callosum in 52%. We evaluated 17 distinct variants. Missense variants in TECPR2 are predominantly located in the N- and C-terminal regions containing β-propeller repeats. Despite constituting nearly half of disease-associated TECPR2 variants, classifying missense variants as (likely) pathogenic according to ACMG criteria remains challenging. We estimate a pathogenic variant carrier frequency of 1/1221 in the general and 1/155 in the Jewish Ashkenazi populations. Based on clinical, neuroimaging, and genetic data, we provide recommendations for variant reporting, clinical assessment, and surveillance/treatment of individuals with TECPR2-associated disorder. This sets the stage for future prospective natural history studies.

Identifiants

DOI: 10.1002/humu.24206 PMID: 33847017
pubmed: 33847017
doi: 10.1002/humu.24206
doi:

Substances chimiques

Carrier Proteins 0
Nerve Tissue Proteins 0
TECPR2 protein, human 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Systematic Review

Langues

eng

Sous-ensembles de citation

IM

Pagination

762-776

Subventions

Organisme : NHGRI NIH HHS
ID : UM1 HG006542
Pays : United States
Organisme : NHGRI NIH HHS
ID : K08 HG008986
Pays : United States
Organisme : NHGRI NIH HHS
ID : U54 HG006542
Pays : United States

Informations de copyright

© 2021 The Authors. Human Mutation published by Wiley Periodicals LLC.

Références

Anazi, S., Maddirevula, S., Salpietro, V., Asi, Y. T., Alsahli, S., Alhashem, A., Shamseldin, AlZahrani, F., Patel, N., Ibrahim, N., Abdulwahab, F. M., Hashem, M., Alhashmi, N., Al Murshedi, F., Al Kindy, A., Alshaer, A., Rumayyan, A., Al Tala, S., Kurdi, W., … Alkuraya, F. S., & H. E. (2017). Expanding the genetic heterogeneity of intellectual disability. Human Genetics, 136(11), 1419-1429. https://doi.org/10.1007/s00439-017-1843-2
Behrends, C., Sowa, M. E., Gygi, S. P., & Harper, J. W. (2010). Network organization of the human autophagy system. Nature, 466(7302), 68-76. https://doi.org/10.1038/nature09204
Cingolani, P., Patel, V. M., Coon, M., Nguyen, T., Land, S. J., Ruden, D. M., & Lu, X. (2012). Using Drosophila melanogaster as a model for genotoxic chemical mutational studies with a new program, SnpSift. Frontiers in Genetics, 3, 35. https://doi.org/10.3389/fgene.2012.00035
Cingolani, P., Platts, A., Wang, L. L., Coon, M., Nguyen, T., Wang, L., Land, S. J., Lu, X., & Ruden, D. M. (2012). A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff: Snps in the genome of Drosophila melanogaster strain w1118; iso-2; iso-3. Fly, 6(2), 80-92. https://doi.org/10.4161/fly.19695
Covone, A. E., Fiorillo, C., Acquaviva, M., Trucco, F., Morana, G., Ravazzolo, R., & Minetti, C. (2016). Wes in a family trio suggests involvement of TECPR2 in a complex form of progressive motor neuron disease: Wes in a family trio suggests involvement of TECPR2. Clinical Genetics, 90(2), 182-185. https://doi.org/10.1111/cge.12730
Ebrahimi-Fakhari, D., Saffari, A., Wahlster, L., Lu, J., Byrne, S., Hoffmann, G. F., Jungbluth, H., & Sahin, M. (2016). Congenital disorders of autophagy: An emerging novel class of inborn errors of neuro-metabolism. Brain, 139(2), 317-337. https://doi.org/10.1093/brain/awv371
Freeman, P. J., Hart, R. K., Gretton, L. J., Brookes, A. J., & Dalgleish, R. (2018). Variantvalidator: Accurate validation, mapping, and formatting of sequence variation descriptions. Human Mutation, 39(1), 61-68. https://doi.org/10.1002/humu.23348
Hahn, K., Rohdin, C., Jagannathan, V., Wohlsein, P., Baumgärtner, W., Seehusen, F., Spitzbarth, I., Grandon, R., Drögemüller, C., & Jäderlund, K. H. (2015). TECPR2 associated neuroaxonal dystrophy in Spanish water dogs. PLOS One, 10(11), e0141824. https://doi.org/10.1371/journal.pone.0141824
Hansen, A. W., Murugan, M., Li, H., Khayat, M. M., Wang, L., Rosenfeld, J., Andrews, B. K., Jhangiani, S. N., Coban Akdemir, Z. H., Sedlazeck, F. J., Ashley-Koch, A. E., Liu, P., Muzny, D. M., Davis, E. E., Katsanis, N., Sabo, A., Posey, J. E., Yang, Y., Wangler, M. F., … Wiener, J. (2019). A genocentric approach to discovery of mendelian disorders. American Journal of Human Genetics, 105(5), 974-986. https://doi.org/10.1016/j.ajhg.2019.09.027
Hebebrand, M., Hüffmeier, U., Trollmann, R., Hehr, U., Uebe, S., Ekici, A. B., Kraus, C., Krumbiegel, M., Reis, A., Thiel, C. T., & Popp, B. (2019). The mutational and phenotypic spectrum of TUBA1A-associated tubulinopathy. Orphanet Journal of Rare Diseases, 14(1), 38. https://doi.org/10.1186/s13023-019-1020-x
Heimer, G., Oz-Levi, D., Eyal, E., Edvardson, S., Nissenkorn, A., Ruzzo, E. K., Szeinberg, A., Maayan, C., Mai-Zahav, M., Efrati, O., Pras, E., Reznik-Wolf, H., Lancet, D., Goldstein, D. B., Anikster, Y., Shalev, S. A., Elpeleg, O., & Ben Zeev, B. (2016). TECPR2 mutations cause a new subtype of familial dysautonomia like hereditary sensory autonomic neuropathy with intellectual disability. European Journal of Paediatric Neurology, 20(1), 69-79. https://doi.org/10.1016/j.ejpn.2015.10.003
Heo, L., Park, H., & Seok, C. (2013). Galaxyrefine: Protein structure refinement driven by side-chain repacking. Nucleic Acids Research, 41(W1), W384-W388. https://doi.org/10.1093/nar/gkt458
Jian, X., Boerwinkle, E., & Liu, X. (2014). In silico prediction of splice-altering single nucleotide variants in the human genome. Nucleic Acids Research, 42(22), 13534-13544. https://doi.org/10.1093/nar/gku1206
Karczewski, K. J., Francioli, L. C., Tiao, G., Cummings, B. B., Alföldi, J., Wang, Q., Collins, R. L., Laricchia, K. M., Ganna, A., Birnbaum, D. P., Gauthier, L. D., Brand, H., Solomonson, M., Watts, N. A., Rhodes, D., Singer-Berk, M., England, E. M., Seaby, E. G., Kosmicki, J. A., … MacArthur, D. G. (2020). The mutational constraint spectrum quantified from variation in 141,456 humans. Nature, 581(7809), 434-443. https://doi.org/10.1038/s41586-020-2308-7
Ko, J., Park, H., Heo, L., & Seok, C. (2012). Galaxyweb server for protein structure prediction and refinement. Nucleic Acids Research, 40(W1), W294-W297. https://doi.org/10.1093/nar/gks493
Ko, J., Park, H., & Seok, C. (2012). Galaxytbm: Template-based modeling by building a reliable core and refining unreliable local regions. BMC Bioinformatics, 13, 198. https://doi.org/10.1186/1471-2105-13-198
Köhler, S., Carmody, L., Vasilevsky, N., Jacobsen, J. O. B., Danis, D., Gourdine, J. P., Gargano, M., Matentzoglu, N., McMurry, J. A., Osumi-Sutherland, D., Cipriani, V., Balhoff, J. P., Conlin, T., Blau, H., Baynam, G., Palmer, R., Gratian, D., Dawkins, H., Segal, M., … Robinson, P. N. (2019). Expansion of the Human Phenotype Ontology (HPO) knowledge base and resources. Nucleic Acids Research, 47(D1), D1018-D1027. https://doi.org/10.1093/nar/gky1105
Liu, X., Jian, X., & Boerwinkle, E. (2013). Dbnsfp v2.0: A database of human non-synonymous SNVs and their functional predictions and annotations. Human Mutation, 34(9), E2393-E2402. https://doi.org/10.1002/humu.22376
Lupski, J. R., Belmont, J. W., Boerwinkle, E., & Gibbs, R. A. (2011). Clan genomics and the complex architecture of human disease. Cell, 147(1), 32-43. https://doi.org/10.1016/j.cell.2011.09.008
Menzies, F. M., Fleming, A., Caricasole, A., Bento, C. F., Andrews, S. P., Ashkenazi, A., Füllgrabe, J., Jackson, A., Jimenez Sanchez, M., Karabiyik, C., Licitra, F., Lopez Ramirez, A., Pavel, M., Puri, C., Renna, M., Ricketts, T., Schlotawa, L., Vicinanza, M., Won, H., … Rubinsztein, D. C. (2017). Autophagy and neurodegeneration: Pathogenic mechanisms and therapeutic opportunities. Neuron, 93(5), 1015-1034. https://doi.org/10.1016/j.neuron.2017.01.022
Meyer, M. J., Lapcevic, R., Romero, A. E., Yoon, M., Das, J., Beltrán, J. F., Mort, M., Stenson, P. D., Cooper, D. N., Paccanaro, A., & Yu, H. (2016). Mutation3d: Cancer gene prediction through atomic clustering of coding variants in the structural proteome. Human Mutation, 37(5), 447-456. https://doi.org/10.1002/humu.22963
Oz-Levi, D., Ben-Zeev, B., Ruzzo, E. K., Hitomi, Y., Gelman, A., Pelak, K., Anikster, Y., Reznik-Wolf, H., Bar-Joseph, I., Olender, T., Alkelai, A., Weiss, M., Ben-Asher, E., Ge, D., Shianna, K. V., Elazar, Z., Goldstein, D. B., Pras, E., & Lancet, D. (2012). Mutation in TECPR2 reveals a role for autophagy in hereditary spastic paraparesis. American Journal of Human Genetics, 91(6), 1065-1072. https://doi.org/10.1016/j.ajhg.2012.09.015
Oz-Levi, D., Gelman, A., Elazar, Z., & Lancet, D. (2013). TECPR2: A new autophagy link for neurodegeneration. Autophagy, 9(5), 801-802. https://doi.org/10.4161/auto.23961
Patwari, P. P., Wolfe, L. F., Sharma, G. D., & Berry-Kravis, E. (2020). TECPR2 mutation associated respiratory dysregulation: More than central apnea. Journal of Clinical Sleep Medicine, 16, 977-982. https://doi.org/10.5664/jcsm.8434
Popp, B., Ekici, A. B., Thiel, C. T., Hoyer, J., Wiesener, A., Kraus, C., Reis, A., & Zweier, C. (2017). Exome Pool-Seq in neurodevelopmental disorders. European Journal of Human Genetics: EJHG, 25(12), 1364-1376. https://doi.org/10.1038/s41431-017-0022-1
Popp, B., & Neuser, S. (2020). Tecpr2 protein models predicted by three algorithms. https://doi.org/10.5281/zenodo.4050472
Rentzsch, P., Witten, D., Cooper, G. M., Shendure, J., & Kircher, M. (2019). Cadd: Predicting the deleteriousness of variants throughout the human genome. Nucleic Acids Research, 47(D1), D886-D894. https://doi.org/10.1093/nar/gky1016
Richards, S., Aziz, N., Bale, S., Bick, D., Das, S., Gastier-Foster, J., Grody, W. W., Hegde, M., Lyon, E., Spector, E., Voelkerding, K., & Rehm, H. L. (2015). Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genetics in Medicine, 17(5), 405-424. https://doi.org/10.1038/gim.2015.30
Sobreira, N., Schiettecatte, F., Valle, D., & Hamosh, A. (2015). Genematcher: A matching tool for connecting investigators with an interest in the same gene. Human Mutation, 36(10), 928-930. https://doi.org/10.1002/humu.22844
Stadel, D., Millarte, V., Tillmann, K. D., Huber, J., Tamin-Yecheskel, B. C., Akutsu, M., Demishtein, A., Anikster, Y., Perez, F., Dötsch, V., Elazar, Z., Rogov, V., Farhan, H., & Behrends, C. (2015). Tecpr2 cooperates with LC3C to regulate COPII-dependent ER export. Molecular Cell, 60(1), 89-104. https://doi.org/10.1016/j.molcel.2015.09.010
Teinert, J., Behne, R., Wimmer, M., & Ebrahimi-Fakhari, D. (2019). Novel insights into the clinical and molecular spectrum of congenital disorders of autophagy. Journal of Inherited Metabolic Disease, 43(1), 1-12. https://doi.org/10.1002/jimd.12084
Wildeman, M., van Ophuizen, E., den Dunnen, J. T., & Taschner, P. E. M. (2008). Improving sequence variant descriptions in mutation databases and literature using the Mutalyzer sequence variation nomenclature checker. Human Mutation, 29(1), 6-13. https://doi.org/10.1002/humu.20654
Xiong, H. Y., Alipanahi, B., Lee, L. J., Bretschneider, H., Merico, D., Yuen, R. K. C., Hua, Y., Gueroussov, S., Najafabadi, H. S., Hughes, T. R., Morris, Q., Barash, Y., Krainer, A. R., Jojic, N., Scherer, S. W., Blencowe, B. J., & Frey, B. J. (2015). Rna splicing. The human splicing code reveals new insights into the genetic determinants of disease. Science, 347(6218), 1254806. https://doi.org/10.1126/science.1254806
Yang, J., Anishchenko, I., Park, H., Peng, Z., Ovchinnikov, S., & Baker, D. (2020). Improved protein structure prediction using predicted interresidue orientations. Proceedings of the National Academy of Sciences of the United States of America, 117(3), 1496-1503. https://doi.org/10.1073/pnas.1914677117
Zech, M., Jech, R., Boesch, S., Škorvánek, M., Weber, S., Wagner, M., Zhao, C., Jochim, A., Necpál, J., Dincer, Y., Vill, K., Distelmaier, F., Stoklosa, M., Krenn, M., Grunwald, S., Bock-Bierbaum, T., Fečíková, A., Havránková, P., Roth, J., … Winkelmann, J. (2020). Monogenic variants in dystonia: An exome-wide sequencing study. The Lancet, Neurology, 19(11), 908-918. https://doi.org/10.1016/S1474-4422(20)30312-4
Zhu, X., Petrovski, S., Xie, P., Ruzzo, E. K., Lu, Y. F., McSweeney, K. M., Ben-Zeev, B., Anikster, Y., Oz-Levi, D., Dhindsa, R. S., Hitomi, Y., Schoch, K., Spillmann, R. C., Heimer, G., Marek-Yagel, D., Tzadok, M., Han, Y., Worley, G., Goldstein, J., … Oldstein, & D. B. (2015). Whole-exome sequencing in undiagnosed genetic diseases: Interpreting 119 trios. Genetics in Medicine, 17(10), 774-781. https://doi.org/10.1038/gim.2014.191

Auteurs

Sonja Neuser (S)

Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany.
ORCID: 0000-0002-2875-8791

Barbara Brechmann (B)

Department of Neurology, The F.M. Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Department of Pediatrics, Hospital for Children and Adolescents, Heidelberg University Hospital, Heidelberg, Germany.
ORCID: 0000-0003-1228-4349

Gali Heimer (G)

Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Ramat Gan, Israel.
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
ORCID: 0000-0001-6218-3170

Ines Brösse (I)

Department of Pediatrics, Hospital for Children and Adolescents, Heidelberg University Hospital, Heidelberg, Germany.

Susanna Schubert (S)

Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany.

Lauren O'Grady (L)

Department of Pediatrics, Division of Medical Genetics and Metabolism, Massachusetts General Hospital, Boston, Massachusetts, USA.

Michael Zech (M)

Institute of Neurogenomics, Helmholtz Zentrum München, Munich, Germany.
Institute of Human Genetics, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.

Siddharth Srivastava (S)

Department of Neurology, The F.M. Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

David A Sweetser (DA)

Department of Pediatrics, Division of Medical Genetics and Metabolism, Massachusetts General Hospital, Boston, Massachusetts, USA.
ORCID: 0000-0002-1621-3284

Yasemin Dincer (Y)

Lehrstuhl für Sozialpädiatrie, Department of Pediatrics, Technische Universität München, Germany.
Zentrum für Humangenetik und Laboratoriumsdiagnostik (MVZ), Martinsried, Germany.

Volker Mall (V)

Lehrstuhl für Sozialpädiatrie, Department of Pediatrics, Technische Universität München, Germany.
kbo-Kinderzentrum München, Munich, Germany.

Juliane Winkelmann (J)

Institute of Neurogenomics, Helmholtz Zentrum München, Munich, Germany.
Institute of Human Genetics, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.
Lehrstuhl für Neurogenetik, Technische Universität München, Munich, Germany.
Munich Cluster for Systems Neurology (Synergy), Ludwig-Maximilians-Universität München, Munich, Germany.

Christian Behrends (C)

Munich Cluster for Systems Neurology (Synergy), Ludwig-Maximilians-Universität München, Munich, Germany.
ORCID: 0000-0002-9184-7607

Basil T Darras (BT)

Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Robert J Graham (RJ)

Department of Anesthesia, Critical Care and Pain Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Parul Jayakar (P)

Nicklaus Children's Hospital, Miami, Florida, USA.

Barry Byrne (B)

Powell Gene Therapy Center, University of Florida, Gainesville, Florida, USA.

Bat El Bar-Aluma (BE)

Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Ramat Gan, Israel.
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Yael Haberman (Y)

Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Ramat Gan, Israel.
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.

Amir Szeinberg (A)

Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Ramat Gan, Israel.
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Hesham M Aldhalaan (HM)

Department of Translational Genomics, Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.

Mais Hashem (M)

Department of Translational Genomics, Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.

Amal Al Tenaiji (A)

Sheikh Khalifa Medical City, Abu Dhabi, United Arab Emirates.

Omar Ismayl (O)

Sheikh Khalifa Medical City, Abu Dhabi, United Arab Emirates.

Asma E Al Nuaimi (AE)

Sheikh Khalifa Medical City, Abu Dhabi, United Arab Emirates.

Karima Maher (K)

Sheikh Khalifa Medical City, Abu Dhabi, United Arab Emirates.

Shahnaz Ibrahim (S)

Department of Paediatrics and Child Health, Aga Khan University Hospital, Karachi, Pakistan.

Fatima Khan (F)

Department of Paediatrics and Child Health, Aga Khan University Hospital, Karachi, Pakistan.

Henry Houlden (H)

Department of Neuromuscular Disorders, Queen Square Institute of Neurology, University College London, London, UK.

Vijayalakshmi S Ramakumaran (VS)

Oxford Centre for Genomic Medicine, Oxford, UK.

Alistair T Pagnamenta (AT)

NIHR Biomedical Research Centre, Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
ORCID: 0000-0001-7334-0602

Jennifer E Posey (JE)

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
ORCID: 0000-0003-4814-6765

James R Lupski (JR)

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
Texas Children's Hospital, Houston, Texas, USA.
Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA.
ORCID: 0000-0001-9907-9246

Wen-Hann Tan (WH)

Division of Genetics and Genomics, Boston Children's Hospital, Boston, Massachusetts, USA.
ORCID: 0000-0002-1593-6149

Gehad ElGhazali (G)

Sheikh Khalifa Medical City, Abu Dhabi, United Arab Emirates.

Isabella Herman (I)

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
Texas Children's Hospital, Houston, Texas, USA.
Department of Pediatrics, Section of Pediatric Neurology and Developmental Neuroscience, Baylor College of Medicine, Houston, Texas, USA.
ORCID: 0000-0002-7359-6832

Tatiana Muñoz (T)

Facultad de Medicina, Clinica Alemana Universidad del Desarrollo, Santiago, Chile.

Gabriela M Repetto (GM)

Facultad de Medicina, Clinica Alemana Universidad del Desarrollo, Santiago, Chile.
ORCID: 0000-0003-0120-5684

Angelika Seitz (A)

Department of Diagnostic and Interventional Radiology, Heidelberg University Hospital, Heidelberg, Germany.

Mandy Krumbiegel (M)

Institute of Human Genetics, Friedrich-Alexander-Universität (FAU), Erlangen, Germany.

Maria Cecilia Poli (MC)

Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
Facultad de Medicina, Clinica Alemana Universidad del Desarrollo, Santiago, Chile.
ORCID: 0000-0001-6817-0573

Usha Kini (U)

Oxford Centre for Genomic Medicine, Oxford, UK.
ORCID: 0000-0001-9111-5433

Stephanie Efthymiou (S)

Department of Neuromuscular Disorders, Queen Square Institute of Neurology, University College London, London, UK.
ORCID: 0000-0003-4900-9877

Jens Meiler (J)

Department of Chemistry, Vanderbilt University, Nashville, Tennessee, USA.
Institute for Drug Discovery, University of Leipzig Medical Center, Leipzig, Germany.
ORCID: 0000-0001-8945-193X

Reza Maroofian (R)

Department of Neuromuscular Disorders, Queen Square Institute of Neurology, University College London, London, UK.
ORCID: 0000-0001-6763-1542

Fowzan S Alkuraya (FS)

Department of Translational Genomics, Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
Department of Anatomy and Cell Biology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.
ORCID: 0000-0003-4158-341X

Rami Abou Jamra (R)

Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany.
ORCID: 0000-0002-1542-1399

Bernt Popp (B)

Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany.
ORCID: 0000-0002-3679-1081

Bruria Ben-Zeev (B)

Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Ramat Gan, Israel.
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Darius Ebrahimi-Fakhari (D)

Department of Neurology, The F.M. Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
ORCID: 0000-0002-0026-4714

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adolescent › Clinical, neuroimaging, and molecular spectrum...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines de transport › Clinical, neuroimaging, and molecular spectrum...
questionsmedicales.fr › Personnes › Tranches d'âge › Enfant › Clinical, neuroimaging, and molecular spectrum...
questionsmedicales.fr › Personnes › Tranches d'âge › Enfant › Enfant d'âge préscolaire › Clinical, neuroimaging, and molecular spectrum...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études de cohortes › Clinical, neuroimaging, and molecular spectrum...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études transversales › Clinical, neuroimaging, and molecular spectrum...
questionsmedicales.fr › Sciences sociales › Sociologie › Facteurs sociologiques › Famille › Clinical, neuroimaging, and molecular spectrum...
questionsmedicales.fr › Malformations et maladies congénitales, héréditaires et néonatales › Maladies génétiques congénitales › Maladies neurodégénératives héréditaires › Neuropathies héréditaires sensitives et autonomes › Clinical, neuroimaging, and molecular spectrum...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Clinical, neuroimaging, and molecular spectrum...
questionsmedicales.fr › Personnes › Tranches d'âge › Nourrisson › Clinical, neuroimaging, and molecular spectrum...
questionsmedicales.fr › Troubles mentaux › Troubles du développement neurologique › Déficience intellectuelle › Clinical, neuroimaging, and molecular spectrum...
questionsmedicales.fr › Diagnostic › Techniques et procédures diagnostiques › Imagerie diagnostique › Tomographie › Imagerie par résonance magnétique › Clinical, neuroimaging, and molecular spectrum...
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles moléculaires › Clinical, neuroimaging, and molecular spectrum...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Mutation › Mutation faux-sens › Clinical, neuroimaging, and molecular spectrum...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines de tissu nerveux › Clinical, neuroimaging, and molecular spectrum...
questionsmedicales.fr › Techniques d'investigation › Neuroimagerie › Clinical, neuroimaging, and molecular spectrum...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Pedigree › Clinical, neuroimaging, and molecular spectrum...
questionsmedicales.fr › Phénomènes génétiques › Phénotype › Clinical, neuroimaging, and molecular spectrum...
questionsmedicales.fr › Phénomènes chimiques › Phénomènes biochimiques › Conformation moléculaire › Conformation des protéines › Clinical, neuroimaging, and molecular spectrum...