| Title: |
Further delineation of the SCAF4-associated neurodevelopmental disorder |
| Authors: |
Schmid, C.M.; Gregor, A.; Ruiz, Anna; Manso Bazús, C.; Herman, I.; Ammouri, F.; Kotzaeridou, U.; McNiven, V.; Dupuis, L.; Steindl, K.; Begemann, A.; Rauch, Anita; 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, Julia; Brunet, Theresa; Riedhammer, K.M.; Elloumi, Houda Z.; Person, Richard; Zou, Fanggeng; Kahle, Juliette J.; Cremer, Kirsten; Schmidt, Axel; Delrue, Marie-Ange; Almeida, Pedro M.; Ramos, Fabiana; Srivastava, Siddharth; Quinlan, Aisling; Robertson, Stephen; Manka, Eva; Kuechler, Alma; Spranger, Stephanie; Nowaczyk, Malgorzata J. M.; Elshafie, Reem M.; Alsharhan, Hind; Hillman, Paul R.; Dunnington, Leslie A.; Braakman, Hilde M. H.; McKee, Shane; Moresco, Angelica; Ignat, Andrea-Diana; Newbury-Ecob, Ruth; Banneau, Guillaume; Patat, Olivier; Kuerbitz, Jeffrey; Rzucidlo, Susan; Sell, Susan S.; Gordon, Patricia; Schuhmann, S.; Reis, André; Halleb, Yosra; Stoeva, Radka; Keren, Boris; Al Masseri, Zainab; Tumer, Zeynep; Hammer-Hansen, Sophia; Krüger Sølyst, Sofus; Steigerwald, Connolly G.; Abreu, Nicolas J.; Faust, Helene; Müller-Nedebock, Amica; Tran Mau-Them, Frederic; Sticht, Heinrich; Universitat Autònoma de Barcelona. Departament de Medicina |
| Contributors: |
Zweier, Christiane |
| Publication Year: |
2024 |
| Collection: |
Universitat Autònoma de Barcelona: Dipòsit Digital de Documents de la UAB |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| ISSN: |
14765438 |
| Relation: |
Instituto de Salud Carlos III PI19/01902; European Commission 3HP-HP-FPA ERN-01-2016/739516; European Journal of Human Genetics; Vol. 33 (December 2024), p. 588-594; https://ddd.uab.cat/record/319548; urn:oai:ddd.uab.cat:319548; urn:scopus_id:85211941491; urn:articleid:14765438v33p588; urn:pmid:39668183; urn:pmcid:PMC12048650; urn:oai:pubmedcentral.nih.gov:12048650 |
| Availability: |
https://ddd.uab.cat/record/319548 |
| Rights: |
open access ; 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. ; https://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.27FCE3BB |
| Database: |
BASE |