This report describes Fliedner-Zweier syndrome (FZS), a newly defined and variable neurodevelopmental syndrome caused by heterozygous mutations in the SCAF4 gene (autosomal dominant). The protein encoded by SCAF4 acts primarily to prevent early mRNA termination during transcription. There is a single orthologous gene in Drosophila, Isha, for which RNAi-targeting constructs, alleles caused by insertional mutagenesis, overexpression constructs and other genetic reagents have been generated. Isha is also orthologous to a second human gene, SCAF8.
The human SCAF4 gene has not been introduced into flies.
RNAi-mediated knockdown of Isha results in impaired locomotor function, learning, and short-term memory; an increased number of active zones in larval neuromuscular junctions is observed.
[updated Apr. 2024 by FlyBase; FBrf0222196]
[FLIEDNER-ZWEIER SYNDROME; FZS](https://omim.org/entry/620511)
[SR-RELATED C-TERMINAL DOMAIN-ASSOCIATED FACTOR 4; SCAF4](https://omim.org/entry/616023)
Eight individuals studied exhibited developmental delay and intellectual disability, mostly in the mild range. Speech was more severely affected than motor development. Behavioral anomalies were reported in five individuals and included autistic features, hyperactivity, and aggressive behavior. Seizures occurred in four individuals. Minor but unspecific facial dysmorphism was noted in most of the individuals. (Fliedner et al., 2020; FBrf0246629)
Fliedner-Zweier syndrome (FZS) is a neurodevelopmental disorder characterized by variable manifestations including mild intellectual disability, seizures, behavioral abnormalities, and various skeletal and structural anomalies (Fliedner et al., 2020; pubmed:32730804; FBrf0246629). [from MIM:620511; 2024.04.02]
Disruptive germline variants in SCAF4 were observed, including splice-site and truncating variants, in the N-terminal two thirds of the protein; heterozygous. Eight variants occurred de novo, and one was inherited. (Fliedner et al., 2020; FBrf0246629)
Fliedner-Zweier syndrome (FZS) is caused by heterozygous mutation in the SCAF4 gene. [from MIM:620511; 2024.04.02]
The protein encoded by SCAF4 acts primarily as an anti-terminator required to prevent early mRNA termination during transcription. Together with SCAF8, acts by suppressing the use of early, alternative poly(A) sites, thereby preventing the accumulation of non-functional truncated proteins. [Gene Cards, SCAF4; 2020.10.22]
Many to one: 2 human genes to 1 Drosophila gene.
Moderate-to high-scoring ortholog of human SCAF4 and SCAF8 (1 Drosophila to 2 human). Dmel\CG4266 shares 29-31% identity and 40-41% similarity with the human genes.
