The human RNA-binding protein (RBP) gene CSDE1 was identified in a genome-wide association study as a potential susceptibility locus for an autism spectrum disorder (ASD; FBhh0000514.)
There is a high-ranking ortholog of human CSDE1 in Drosophila, Unr. Several alleles of Unr have been generated, including RNAi targeting constructs, fluorescently tagged constructs, and misexpression constructs generated by insertional mutagenesis.
The human gene Hsap\CSDE1 has been introduced into flies.
In Unr loss-of-function hypomorphs, the neuromuscular junction (NMJ) of A1-7 lateral longitudinal muscle 1 shows an increase in both total bouton number and satellite bouton number, as well as defective endocytosis. Electrophysiological assays show that Unr hypomorphs have impaired synaptic transmission (lower excitatory junction potential frequency). Pan-neuronal RNAi knockdown shows a similar synaptic overgrowth phenotype to the hypomorph. This can be rescued by overexpression of Unr or the human gene Hsap\CSDE1, indicating that Hsap\CSDE1 it is capable of heterologous rescue (functional complementation).
[updated Jan 2020 by FlyBase; FBrf0222196]
Autism, the prototypic pervasive developmental disorder (PDD), is usually apparent by 3 years of age. It is characterized by a triad of limited or absent verbal communication, a lack of reciprocal social interaction or responsiveness, and restricted, stereotypic, and ritualized patterns of interests and behavior (Bailey et al., 1996, pubmed:8655659; Risch et al., 1999, pubmed:10417292). 'Autism spectrum disorder,' sometimes referred to as ASD, is a broader phenotype encompassing the less severe disorders Asperger syndrome (OMIM:608638) and pervasive developmental disorder, not otherwise specified (PDD-NOS). 'Broad autism phenotype' includes individuals with some symptoms of autism, but who do not meet the full criteria for autism or other disorders. Mental retardation coexists in approximately two-thirds of individuals with ASD, except for Asperger syndrome, in which mental retardation is conspicuously absent (Jones et al., 2008; pubmed:18698615). [from OMIM:209850; 2017.03.18]
The most consistent phenotypes of individuals with CSDE1 mutations include ASD, intellectual disability (ID), delayed speech, and delayed motor development. Of the 16 individuals for whom cognitive ability was assessed, 14 had a diagnosis of mild-to-severe ID and the remaining 2 patients had cognitive performance in the below-average range of intellectual functioning. In addition, we noted several common comorbidities : recurrent seizures or epilepsy (44%), increased head circumference or macrocephaly (43%), anxiety behavior (54%), attention-deficit/hyperactivity disorder (69%), variable ocular abnormalities (54%), hand development abnormalities (40%), and hypotonia (46%). (Adapted from Guo et al. 2019 and references therein, FBrf0243646.)
The SFARI Gene autism database ( https:gene.sfari.org ) rates the gene-autism association for CSDE1 as high confidence (score 1). [2020.11.05]
Enrichment and pathway analyses have shown that ASD risk genes are frequently associated with transcriptional regulation, especially targets of RNA binding proteins (RBPs) such as CSDE1. RBPs mainly function in posttranscriptional gene regulation, which is essential to sustain cellular metabolism, and to coordinate maturation, transport, stability, and degradation of all classes of RNAs. CSDE1, also known as UNR, encodes a highly conserved RBP containing five cold-shock domains and has been implicated in both neuronal migration and differentiation. (Adapted from Guo et al. 2019 and references therein, FBrf0243646.)