This report describes intellectual disability, syndromic, autosomal dominant, SRSF1-related, an automosomal dominant syndromic intellectual disability with developmental delay and intellectual disability, hypotonia, neurobehavioral problems, and variable skeletal and cardiac anomalies. The human gene implicated is SRSF1, which encodes serine and arginine rich splicing factor 1, which plays a role in preventing exon skipping, ensuring the accuracy of splicing and regulating alternative splicing mRNA. There is one high-scoring fly ortholog, Dmel\SF2, for which classical alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated.
UAS constructs of the human Hsap\SRSF1 gene, including wild-type SRSF1 and multiple variants implicated in disease, have been introduced into flies. See the 'Disease-Implicated Variants' table below.
Eye-specific overexpression of wild-type Hsap\SRSF1 or Dmel\SF2 phenotypic results in changes in the eye that are attributable to alternative splicing of key genes involved in eye development (FBrf0201668; FBrf0256462). This overexpression phenotype is ameliorated by coexpression of splicing-inactive Hsap\SRSF1 variants.
[updated Apr. 2024 by FlyBase; FBrf0222196]
[NEURODEVELOPMENTAL DISORDER WITH DYSMORPHIC FACIES AND BEHAVIORAL ABNORMALITIES; NEDFBA](https://omim.org/entry/620489)
[SPLICING FACTOR, SERINE/ARGININE-RICH, 1; SRSF1](https://omim.org/entry/600812)
Neurodevelopmental disorder with dysmorphic facies and behavioral abnormalities (NEDFBA) is characterized by developmental delay with variably impaired intellectual development with speech delay, behavioral abnormalities, and nonrecurrent dysmorphic facial features. Additional features may include hypotonia, skeletal anomalies such as scoliosis or pectus defects, and visual problems such as strabismus and myopia (Bogaert, et al., 2023, pubmed:37071997; FBrf0256462). [from MIM:620489; 2023.09.05]
Neurodevelopmental disorder with dysmorphic facies and behavioral abnormalities (NEDFBA) is caused by heterozygous mutation in the SRSF1 gene on chromosome 17q22. [from MIM:620489; 2023.09.05]
SRSF1 encodes a member of the arginine/serine-rich splicing factor protein family. The encoded protein can either activate or repress mRNA splicing, depending on its phosphorylation state and its interaction partners. [provided by RefSeq, Jun 2014]
Two to one (2 human to 1 Drosophila); SRSF1 has one high-scoring Drosophila ortholog, SF2.
High-scoring ortholog of human SRSF1, moderate scoring ortholog of human SRSF9 (1 Drosophila to 2 human).
