| Date | Panel | Item | Activity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Intellectual disability - microarray and sequencing v2.588 | TBC1D20 |
Konstantinos Varvagiannis gene: TBC1D20 was added gene: TBC1D20 was added to Intellectual disability. Sources: Literature,Radboud University Medical Center, Nijmegen Mode of inheritance for gene: TBC1D20 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TBC1D20 were set to 24239381; 26063829 Phenotypes for gene: TBC1D20 were set to Warburg Micro syndrome 4 (MIM 615663) Penetrance for gene: TBC1D20 were set to Complete Review for gene: TBC1D20 was set to GREEN gene: TBC1D20 was marked as current diagnostic Added comment: Biallelic pathogenic variants in TBC1D20 cause Warburg Micro syndrome 4 (MIM 615663). --------- Liegel et al. (PMID: 24239381) report on 7 individuals from 5 unrelated families. ID was a universal feature along with opthalmological, endocrine and other neurological features of the disorder. Seizures were noted in 4 individuals from 2 families. Table S4 of this article provides clinical details on each subject. All affected individuals were homozygous for LoF variants, private to each family. 3 nonsense variants, 1 frameshift one as well as an intragenic deletion (exons 2-8) were identified. These subjects belonged to a cohort of 77 individuals with suspected Warburg Micro syndrome (WMS) or disorders of the same spectrum (eg. Martsof syndrome). Screening for TBC1D20 mutations in these individuals was performed after identification of a homozygous LoF Tbc1d20 mutation in blind sterile mice, presenting a phenotype somewhat similar to WMS (congenital cataracts and testicular anomalies). Alternative causes of WM (eg. pathogenic variants in RAB3GAP1, RAB3GAP2 and RAB18) had previously been excluded in this cohort. The authors demonstrated aberrant lipid droplet formation in embryonic fibroblasts from blind sterile mice as well as in fibroblasts from individuals with a diagnosis of WMS due to mutations in either of TBC1D20, RAB18 and RAB3GAP1. --------- TBC1D20 is included in the DD panel of G2P, associated with Warburg micro syndrome 4 (Disease confidence: probable / ID among the phenotypes assigned to this entry). This gene is included in gene panels for ID offered by different diagnostic laboratories (incl. Radboudumc). --------- As a result, TBC1D20 can be considered for inclusion in the ID panel as green (or amber). Sources: Literature, Radboud University Medical Center, Nijmegen |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing | RAB3GAP1 | BRIDGE consortium edited their review of RAB3GAP1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing | RAB3GAP1 | BRIDGE consortium edited their review of RAB3GAP1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing | RAB3GAP1 | BRIDGE consortium reviewed RAB3GAP1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||