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Intellectual disability

Gene: CSDE1

Green List (high evidence)

CSDE1 (cold shock domain containing E1)
EnsemblGeneIds (GRCh38): ENSG00000009307
EnsemblGeneIds (GRCh37): ENSG00000009307
OMIM: 191510, Gene2Phenotype
CSDE1 is in 1 panel

2 reviews

Catherine Snow (Genomics England)

Comment on list classification: CSDE1 identified by Konstantinos Varvagiannis based on a publication by Guo et al. (PMID: 31579823) This is the first time CSDE1 has been associated with any diseases therefore it not currently in OMIM or Gene2Phenotype. However consistent phenotype of DD/ID and autism seen among all individuals with variants. With functional work on both mice and Drosophila.
Created: 24 Oct 2019, 4:23 p.m. | Last Modified: 24 Oct 2019, 4:23 p.m.
Panel Version: 2.1086

Konstantinos Varvagiannis (Other)

Green List (high evidence)

Guo et al. (2019 - DOI: 10.1126/sciadv.aax2166) report on 18 individuals from 18 unrelated families, with heterozygous likely gene disrupting (stopgain/frameshift/spice-site) CSDE1 variants.

Initial sequencing with MIPs found in 3 individuals from an autism cohort (4045 probands), while subsequent targeted sequencing of a larger cohort (autism spectrum/ID network) led to identification of 5 additional relevant individuals and Genematcher/collaborations a further 10 (the latter by WES).

Consistent phenotypes included ASD (10 of 15 formally evaluated), DD (motor: 15/17 - speech: 17/17) and ID (mild to severe in 14 of 16 assessed, in further 2 in the below-average range). Recurrent seizures or epilepsy were reported for 7 of 16 patients. Other variable features were anxiety or ADHD, increased OFC, ocular, hand and MRI anomalies.

The study was mainly focused on LGD variants with p.R123* (NM_001242891.1:c.367C>T) being a reccurrent one, found in 3 families.

8 of these variants were de novo, 8 further inherited (often from a less severely affected parent, although parental neuropsychiatric status was not available for individuals from all 3 groups). In 2 cases inheritance was unknown (only 1 parental sample available).

3 individuals with de novo missense variants were also identified. Features in those individuals also included ASD and/or DD and ID (2/3) [Table S1].

Arguments to support involvement of the CSDE1 variants included the:
- role of the gene encoding an RNA binding protein implicated in neuronal migration/differentiation (cited : 24012837, 29129916),
- statistically significant burden of the variants in the cohorts examined,
- relevant CSDE1 intolerance scores (pLI of 1 and %RVIS of 6.18),
- relevant human (mRNA) / mouse (protein) spatial and temporal expression patterns,
- exclusion of apparent alternative diagnoses to the extent possible in many subjects with CNVs/SNVs/ROH of uncertain significance in very few,
- cosegregation with rather similar neuropsychiatric phenotypes in case of carrier parents,
- enrichment of ASD-related genes (and FMRP targets) among CSDE1-binding targets,
- suppression of Ctnnb1 expression (at the protein level) affecting Wnt/β-catenin signalling,
- effect of knockdown and/or mutants in mouse (shRNA) and Drosophila (mt and siRNA) models affecting synapse formation and synaptic transmission,
- rescue of many of the previous phenotypes by expression of human CSDE1 (mice), expression of stabilized β-Catenin (mice) or RNAi-stable-dUNR (Drosophila) [also supporting LoF as the underlying effect of variants].

CSDE1 is not commonly included in gene panels for ID offered by diagnostic laboratories. There is no associated phenotype in OMIM/G2P.

Overall, this gene could be considered for inclusion in the ID panel probably as green (or amber).
Sources: Literature
Created: 28 Sep 2019, 5:37 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Autism; Global developmental delay; Intellectual disability




Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
  • Expert Review Green
  • Autism
  • Global developmental delay
  • Intellectual disability
Clinvar variants
Variants in CSDE1
Panels with this gene

History Filter Activity

3 May 2022, Gel status: 3

Added Tag

Sarah Leigh (Genomics England Curator)

Tag gene-checked tag was added to gene: CSDE1.

24 Oct 2019, Gel status: 3

Entity classified by Genomics England curator

Catherine Snow (Genomics England)

Gene: csde1 has been classified as Green List (High Evidence).

24 Oct 2019, Gel status: 0

Set publications

Catherine Snow (Genomics England)

Publications for gene: CSDE1 were set to

28 Sep 2019, Gel status: 0

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes, Set penetrance

Konstantinos Varvagiannis (Other)

gene: CSDE1 was added gene: CSDE1 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: CSDE1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: CSDE1 were set to Phenotypes for gene: CSDE1 were set to Autism; Global developmental delay; Intellectual disability Penetrance for gene: CSDE1 were set to unknown Review for gene: CSDE1 was set to GREEN