Further delineation of the SCAF4-associated neurodevelopmental disorder
Schmid, C.M. (University of Bern)
Gregor, A. (University of Bern)
Ruiz, Anna (Parc Taulí Hospital Universitari. Institut d'Investigació i Innovació Parc Taulí (I3PT))
Manso Bazús, C. (Parc Taulí Hospital Universitari. Institut d'Investigació i Innovació Parc Taulí (I3PT))
Herman, I. (Baylor College of Medicine (Houston, Estats Units d'Amèrica))
Ammouri, F. (The University of Kansas Health System)
Kotzaeridou, U. (Universitätsklinikum Heidelberg)
McNiven, V. (McMaster Children's Hospital)
Dupuis, L. (University of Toronto)
Steindl, K. (University of Zurich)
Begemann, A. (University of Zurich)
Rauch, Anita (University of Zurich)
Suter, A.A. (University of Zurich)
Isidor, B. (CHU de Nantes)
Mercier, S. (CHU de Nantes)
Nizon, M. (CHU de Nantes)
Cogné, B. (CHU de Nantes)
Deb, W. (CHU de Nantes)
Besnard, T. (CHU de Nantes)
Haack, Tobias B. (Universität Tübingen)
Falb, R.J. (Universität Tübingen)
Müller, A.J. (Universität Tübingen)
Linden, T. (University Children's Hospital)
Haldeman-Englert, C.R. (Mission Fullerton Genetics Center)
Ockeloen, C.W. (Radboud University Medical Center)
Mattioli, F. (University of Lausanne)
Reymond, A. (University of Lausanne)
Ibrahim, N. (Lahore College for Women University)
Naz, S. (Lahore College for Women University)
Lacaze, E. (Le Havre Hospital)
Bassetti, J.A. (Weill Cornell Medicine)
Hoefele, Julia (Technical University of Munich)
Brunet, Theresa (Technical University of Munich)
Riedhammer, K.M. (Technical University of Munich)
Elloumi, Houda Z. (GeneDx (Estats Units d'Amèrica))
Person, Richard (GeneDx (Estats Units d'Amèrica))
Zou, Fanggeng (GeneDx (Estats Units d'Amèrica))
Kahle, Juliette J. (GeneDx (Estats Units d'Amèrica))
Cremer, Kirsten (University of Bonn (Alemanya))
Schmidt, Axel (University of Bonn (Alemanya))
Delrue, Marie-Ange (Sainte-Justine University Hospital (Canadà))
Almeida, Pedro M. (Hospital Pediátrico de Coimbra (Portugal))
Ramos, Fabiana (Centro de Diagnóstico Pré-natal. Unidade Local de Saúde de Coimbra (Portugal))
Srivastava, Siddharth (Boston Children's Hospital and Harvard Medical School (Estats Units d'Amèrica))
Quinlan, Aisling (Boston Children's Hospital and Harvard Medical School (Estats Units d'Amèrica))
Robertson, Stephen (Otago University (Nova Zelanda))
Manka, Eva (Universitätsmedizin Essen (Alemanya))
Kuechler, Alma (Universität Duisburg-Essen (Alemanya))
Spranger, Stephanie (Klinikum Bremen-Mitte (Alemanya))
Nowaczyk, Malgorzata J. M. (McMaster University (Canadà))
Elshafie, Reem M. (Kuwait Medical Genetics Centre)
Alsharhan, Hind (Kuwait University)
Hillman, Paul R. (Children's Memorial Hermann Hospital (Estats Units d' Amèrica))
Dunnington, Leslie A. (Children's Memorial Hermann Hospital (Estats Units d' Amèrica))
Braakman, Hilde M. H. (Radboud University Medical Center & Donders Institute for Brain (Països Baixos))
McKee, Shane (Northern Ireland Regional Genetics Service)
Moresco, Angelica (Western University)
Ignat, Andrea-Diana (Western University)
Newbury-Ecob, Ruth (University Hospitals Bristol (Regne Unit))
Banneau, Guillaume (Toulouse University Hospital (França))
Patat, Olivier (Toulouse University Hospital (França))
Kuerbitz, Jeffrey (Texas Children's Hospital (Estats Units d'Amèrica))
Rzucidlo, Susan (Penn State Health Children's Hospital (Estats Units d'Amèrica))
Sell, Susan S. (Penn State Health Children's Hospital (Estats Units d'Amèrica))
Gordon, Patricia (Penn State Health Children's Hospital (Estats Units d'Amèrica))
Schuhmann, S. (Universität Erlangen-Nürnberg (Alemanya))
Reis, André (Centre for Rare Diseases Erlangen (ZSEER)(Alemanya))
Halleb, Yosra (Le Mans Hospital (França))
Stoeva, Radka (Le Mans Hospital (França))
Keren, Boris (Hôpital Pitié-Salpêtrière (França))
Al Masseri, Zainab (Qatif Central Hospital (Aràbia Saudita))
Tumer, Zeynep (University of Copenhagen)
Hammer-Hansen, Sophia (Copenhagen University Hospital (Dinamarca))
Krüger Sølyst, Sofus (Copenhagen University Hospital (Dinamarca))
Steigerwald, Connolly G. (NYU Grossman School of Medicine (Estats Units d'Amèrica))
Abreu, Nicolas J. (NYU Grossman School of Medicine (Estats Units d'Amèrica))
Faust, Helene (University of Leipzig Medical Center (Alemanya))
Müller-Nedebock, Amica (University of Leipzig Medical Center (Alemanya))
Tran Mau-Them, Frederic (Université de Bourgogne (França))
Sticht, Heinrich (Universität Erlangen-Nürnberg (Alemanya))
Zweier, Christiane col. (Department for Biomedical Research (DBMR). University of Bern)
Universitat Autònoma de Barcelona. Departament de Medicina

Fecha:	2024
Resumen:	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.
Ayudas:	Instituto de Salud Carlos III PI19/01902 European Commission 3HP-HP-FPA ERN-01-2016/739516
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Publicado en:	European Journal of Human Genetics, Vol. 33 (December 2024) , p. 588-594, ISSN 1476-5438

DOI: 10.1038/s41431-024-01760-2
PMID: 39668183

7 p, 1.9 MB

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