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| Intellectual disability - microarray and sequencing v3.1561 | CSDE1 | Sarah Leigh Tag gene-checked tag was added to gene: CSDE1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v2.1086 | CSDE1 | Catherine Snow Classified gene: CSDE1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v2.1086 | CSDE1 | Catherine Snow Added comment: 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. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v2.1086 | CSDE1 | Catherine Snow Gene: csde1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v2.1085 | CSDE1 | Catherine Snow Publications for gene: CSDE1 were set to http://doi.org/10.1126/sciadv.aax2166 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v2.1047 | CSDE1 |
Konstantinos Varvagiannis 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 http://doi.org/10.1126/sciadv.aax2166 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 Added comment: 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 |
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