Further delineation of the SCAF4-associated neurodevelopmental disorder
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| Názov: | Further delineation of the SCAF4-associated neurodevelopmental disorder |
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| Autori: | Cosima M. Schmid, Anne Gregor, Anna Ruiz, Carmen Manso Bazús, Isabella Herman, Farah Ammouri, Urania Kotzaeridou, Vanda McNiven, Lucie Dupuis, Katharina Steindl, Anaïs Begemann, Anita Rauch, Aude-Annick Suter, Bertrand Isidor, Sandra Mercier, Mathilde Nizon, Benjamin Cogné, Wallid Deb, Thomas Besnard, Tobias B. Haack, Ruth J. Falb, Amelie J. Müller, Tobias Linden, Chad R. Haldeman-Englert, Charlotte W. Ockeloen, Francesca Mattioli, Alexandre Reymond, Nazia Ibrahim, Shagufta Naz, Elodie Lacaze, Jennifer A. Bassetti, Julia Hoefele, Theresa Brunet, Korbinian M. Riedhammer, Houda Z. Elloumi, Richard Person, Fanggeng Zou, Juliette J. Kahle, Kirsten Cremer, Axel Schmidt, Marie-Ange Delrue, Pedro M. Almeida, Fabiana Ramos, Siddharth Srivastava, Aisling Quinlan, Stephen Robertson, Eva Manka, Alma Kuechler, Stephanie Spranger, Malgorzata J. M. Nowaczyk, Reem M. Elshafie, Hind Alsharhan, Paul R. Hillman, Leslie A. Dunnington, Hilde M. H. Braakman, Shane McKee, Angelica Moresco, Andrea-Diana Ignat, Ruth Newbury-Ecob, Guillaume Banneau, Olivier Patat, Jeffrey Kuerbitz, Susan Rzucidlo, Susan S. Sell, Patricia Gordon, Sarah Schuhmann, André Reis, Yosra Halleb, Radka Stoeva, Boris Keren, Zainab Al Masseri, Zeynep Tümer, Sophia Hammer-Hansen, Sofus Krüger Sølyst, Connolly G. Steigerwald, Nicolas J. Abreu, Helene Faust, Amica Müller-Nedebock, Frédéric Tran Mau-Them, Heinrich Sticht, Christiane Zweier |
| Prispievatelia: | University of Zurich, Zweier, Christiane |
| Zdroj: | Eur J Hum Genet European Journal of Human Genetics, 33, 5, pp. 588-594 European journal of human genetics, vol. 33, no. 5, pp. 588-594 Schmid, C M, Gregor, A, Ruiz, A, Manso Bazús, C, Herman, I, Ammouri, F, Kotzaeridou, U, McNiven, V, Dupuis, L, Steindl, K, Begemann, A, Rauch, A, Suter, A A, Isidor, B, Mercier, S, Nizon, M, Cogné, B, Deb, W, Besnard, T, Haack, T B, Falb, R J, Müller, A J, Linden, T, Haldeman-Englert, C R, Ockeloen, C W, Mattioli, F, Reymond, A, Ibrahim, N, Naz, S, Lacaze, E, Bassetti, J A, Hoefele, J, Brunet, T, Riedhammer, K M, Elloumi, H Z, Person, R, Zou, F, Kahle, J J, Cremer, K, Schmidt, A, Delrue, M A, Almeida, P M, Ramos, F, Srivastava, S, Quinlan, A, Robertson, S, Manka, E, Kuechler, A, Spranger, S, Nowaczyk, M J M, Elshafie, R M, Alsharhan, H, Hillman, P R, Dunnington, L A, Braakman, H M H, McKee, S, Moresco, A, Ignat, A D, Newbury-Ecob, R, Banneau, G, Patat, O, Kuerbitz, J, Rzucidlo, S, Sell, S S, Gordon, P, Schuhmann, S, Reis, A, Halleb, Y, Stoeva, R, Keren, B, Al Masseri, Z, Tümer, Z, Hammer-Hansen, S, Krüger Sølyst, S, Steigerwald, C G, Abreu, N J, Faust, H, Müller-Nedebock, A, Tran Mau-Them, F, Sticht, H & Zweier, C 2025, ' Further delineation of the SCAF4-associated neurodevelopmental disorder ', European Journal of Human Genetics, vol. 33, no. 5, pp. 588-594 . https://doi.org/10.1038/s41431-024-01760-2 |
| Informácie o vydavateľovi: | Springer Science and Business Media LLC, 2024. |
| Rok vydania: | 2024 |
| Predmety: | Male, Adult, 0301 basic medicine, 2716 Genetics (clinical), Adolescent, 10039 Institute of Medical Genetics, Medizin, Mutation, Missense, 610 Medicine & health, Humans, Female, Neurodevelopmental Disorders/genetics, Neurodevelopmental Disorders/pathology, Child, Preschool, Child, Phenotype, Infant, Article, 03 medical and health sciences, 1311 Genetics, Genetics research, Genetics, Genetics (clinical), 0303 health sciences, Paediatrics - Development and lifelong plasticity, Autism spectrum disorders, Neurodevelopmental Disorders, 570 Life sciences, biology, Human Genetics - Development and lifelong plasticity |
| Popis: | While mostly de novo truncating variants in SCAF4 were recently identified in 18 individuals with variable neurodevelopmental phenotypes, knowledge on the molecular and clinical spectrum is still limited. We assembled data on 50 novel individuals with SCAF4 variants ascertained via GeneMatcher and personal communication. With detailed evaluation of clinical data, in silico predictions and structural modeling, we further characterized the molecular and clinical spectrum of the autosomal dominant SCAF4-associated neurodevelopmental disorder. The molecular spectrum comprises 25 truncating, eight splice-site and five missense variants. While all other truncating variants were classified as pathogenic/likely pathogenic, significance of one C-terminal truncating variant, one splice-site variant and the missense variants remained unclear. Three missense variants in the CTD-interacting domain of SCAF4 were predicted to destabilize the domain. Twenty-three variants occurred de novo, and variants were inherited in 13 cases. Frequent clinical findings were mild developmental delay with speech impairment, seizures, and skeletal abnormalities such as clubfoot, scoliosis or hip dysplasia. Cognitive abilities ranged from normal IQ to severe intellectual disability (ID), with borderline to mild ID in the majority of individuals. Our study confirms the role of SCAF4 variants in neurodevelopmental disorders and further delineates the associated clinical phenotype. |
| Druh dokumentu: | Article Other literature type |
| Popis súboru: | application/pdf; s41431_024_01760_2.pdf - application/pdf |
| Jazyk: | English |
| ISSN: | 1476-5438 1018-4813 |
| DOI: | 10.1038/s41431-024-01760-2 |
| DOI: | 10.5167/uzh-266396 |
| DOI: | 10.48620/84512 |
| Prístupová URL adresa: | https://pubmed.ncbi.nlm.nih.gov/39668183 https://hdl.handle.net/https://repository.ubn.ru.nl/handle/2066/318974 https://hdl.handle.net/2066/318974 https://repository.ubn.ru.nl//bitstream/handle/2066/318974/318974.pdf http://nbn-resolving.org/urn/resolver.pl?urn=urn:nbn:ch:serval-BIB_C4EA3A0740C86 https://serval.unil.ch/notice/serval:BIB_C4EA3A0740C8 https://serval.unil.ch/resource/serval:BIB_C4EA3A0740C8.P001/REF.pdf https://curis.ku.dk/ws/files/449711814/s41431-024-01760-2.pdf https://www.zora.uzh.ch/id/eprint/266396/ https://doi.org/10.5167/uzh-266396 https://www.ncbi.nlm.nih.gov/pubmed/39668183 https://doi.org/10.1038/s41431-024-01760-2 https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&origin=inward&scp=85211941491 |
| Rights: | CC BY |
| Prístupové číslo: | edsair.doi.dedup.....0bbf48de74919174b84360e80c745c7c |
| Databáza: | OpenAIRE |
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Nájsť tento článok vo Web of Science | Abstrakt: | While mostly de novo truncating variants in SCAF4 were recently identified in 18 individuals with variable neurodevelopmental phenotypes, knowledge on the molecular and clinical spectrum is still limited. We assembled data on 50 novel individuals with SCAF4 variants ascertained via GeneMatcher and personal communication. With detailed evaluation of clinical data, in silico predictions and structural modeling, we further characterized the molecular and clinical spectrum of the autosomal dominant SCAF4-associated neurodevelopmental disorder. The molecular spectrum comprises 25 truncating, eight splice-site and five missense variants. While all other truncating variants were classified as pathogenic/likely pathogenic, significance of one C-terminal truncating variant, one splice-site variant and the missense variants remained unclear. Three missense variants in the CTD-interacting domain of SCAF4 were predicted to destabilize the domain. Twenty-three variants occurred de novo, and variants were inherited in 13 cases. Frequent clinical findings were mild developmental delay with speech impairment, seizures, and skeletal abnormalities such as clubfoot, scoliosis or hip dysplasia. Cognitive abilities ranged from normal IQ to severe intellectual disability (ID), with borderline to mild ID in the majority of individuals. Our study confirms the role of SCAF4 variants in neurodevelopmental disorders and further delineates the associated clinical phenotype. |
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| ISSN: | 14765438 10184813 |
| DOI: | 10.1038/s41431-024-01760-2 |