Portal de investigación
Further delineation of the SCAF4-associated neurodevelopmental disorder
Fecha de publicación:
Fecha Ahead of Print:
Autores de I3PT
Participantes ajenos a I3PT
- Schmid, CM
- Gregor, A
- Herman, I
- Ammouri, F
- Kotzaeridou, U
- Mcniven, V
- Dupuis, L
- Steindl, K
- Begemann, A
- Rauch, A
- Suter, AA
- Isidor, B
- Mercier, S
- Nizon, M
- Cogné, B
- Deb, W
- Besnard, T
- Haack, TB
- Falb, RJ
- Müller, AJ
- Linden, T
- Haldeman-Englert, CR
- Ockeloen, CW
- Mattioli, F
- Reymond, A
- Ibrahim, N
- Naz, S
- Lacaze, E
- Bassetti, JA
- Hoefele, J
- Brunet, T
- Riedhammer, KM
- Elloumi, HZ
- Person, R
- Zou, FG
- Kahle, JJ
- Cremer, K
- Schmidt, A
- Delrue, MA
- Almeida, PM
- Ramos, F
- Srivastava, S
- Quinlan, A
- Robertson, S
- Manka, E
- Kuechler, A
- Spranger, S
- Nowaczyk, MJM
- Elshafie, RM
- Alsharhan, H
- Hillman, PR
- Dunnington, LA
- Braakman, HMH
- Mckee, S
- Moresco, A
- Ignat, AD
- Newbury-Ecob, R
- Banneau, G
- Patat, O
- Kuerbitz, J
- Rzucidlo, S
- Sell, SS
- Gordon, P
- Schuhmann, S
- Reis, A
- Halleb, Y
- Stoeva, R
- Keren, B
- Al Masseri, Z
- Tuemer, Z
- Hammer-Hansen, S
- Solyst, SK
- Steigerwald, CG
- Abreu, NJ
- Faust, H
- Mueller-Nedebock, A
- Mau-Them, FT
- Sticht, H
- Zweier, C
Grupos de Investigación
Abstract
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.
Datos de la publicación
- ISSN/ISSNe:
- 1018-4813, 1476-5438
- Tipo:
- Article
- Páginas:
- 588-594
- PubMed:
- 39668183
- Enlace a otro recurso:
- www.scopus.com
EUROPEAN JOURNAL OF HUMAN GENETICS NATURE PUBLISHING GROUP
Citas Recibidas en Web of Science: 2
Documentos
- No hay documentos
Filiaciones
Campos de Estudio
Cita
Schmid CM,Gregor A,Ruiz A,Bazús CM,Herman I,Ammouri F,Kotzaeridou U,Mcniven V,Dupuis L,Steindl K et al. Further delineation of the <i>SCAF4</i>-associated neurodevelopmental disorder. Eur. J. Hum. Genet. 2024. 33. (5):p. 588-594. DOI: 10.1038/s41431-024-01760-2.
Schmid CM,Gregor A,Ruiz A,Bazús CM,Herman I,Ammouri F,Kotzaeridou U,Mcniven V,Dupuis L,Steindl K,Begemann A,Rauch A,Suter AA,Isidor B,Mercier S,Nizon M,Cogné B,Deb W,Besnard T,Haack TB,Falb RJ,Müller AJ,Linden T,Haldeman CR,Ockeloen CW,Mattioli F,Reymond A,Ibrahim N,Naz S,Lacaze E,Bassetti JA,Hoefele J,Brunet T,Riedhammer KM,Elloumi HZ,Person R,Zou FG,Kahle JJ,Cremer K,Schmidt A,Delrue MA,Almeida PM,Ramos F,Srivastava S,Quinlan A,Robertson S,Manka E,Kuechler A,Spranger S,Nowaczyk MJM,Elshafie RM,Alsharhan H,Hillman PR,Dunnington LA,Braakman HMH,Mckee S,Moresco A,Ignat AD,Newbury R,Banneau G,Patat O,Kuerbitz J,Rzucidlo S,Sell SS,Gordon P,Schuhmann S,Reis A,Halleb Y,Stoeva R,Keren B,Al Masseri Z,Tuemer Z,Hammer S,Solyst SK,Steigerwald CG,Abreu NJ,Faust H,Mueller A,Mau FT,Sticht H,Zweier C. Further delineation of the <i>SCAF4</i>-associated neurodevelopmental disorder. Eur. J. Hum. Genet. 2024. 33. (5):p. 588-594. IF:4,600. (1).