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| Early onset or syndromic epilepsy v2.122 | TBC1D2B |
Konstantinos Varvagiannis gene: TBC1D2B was added gene: TBC1D2B was added to Genetic epilepsy syndromes. Sources: Literature Mode of inheritance for gene: TBC1D2B was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TBC1D2B were set to 32623794 Phenotypes for gene: TBC1D2B were set to Global developmental delay; Intellectual disability; Seizures; Gingival overgrowth; Behavioral abnormality; Abnormality of the mandible; Abnormality of brain morphology; Abnormality of the eye; Hearing abnormality Penetrance for gene: TBC1D2B were set to Complete Review for gene: TBC1D2B was set to GREEN Added comment: Harms et al (2020 - PMID: 32623794) report on 3 unrelated individuals with biallelic pLoF TBC1D2B variants. Features included cognitive impairment (mild ID in one case, regression at the age of 12y in another, hypotonia and delayed milestones in a third aged 8m), seizures (3/3 - variable age of onset) and/or gingival overgrowth (2/3 - prior to initiation of AEDs). Other findings included behavioral abnormalities, mandibular anomalies, abnormal brain imaging and ophthalmologic or (rarely) audiometric evaluations. All were born to non-consanguineous couples and additional investigations were performed in some. Variants were identified by WES or trio WGS, with Sanger confirmation/compatible segregation analyses. In line with the pLoF variants, mRNA studies in fibroblasts from 2 unrelated affected individuals demonstrated significantly reduced (~80-90%) TBC1C2D mRNA levels compared to controls, restored following cycloheximide treatment. Protein was absent in patient fibroblasts. TBC-domain containing GTPase activating proteins are known as key regulators of RAB GTPase activity. TBC1D2B was shown to colocalize with RAB5-positive endocytic vesicles. CRISPR/Cas9-mediated ko of TBC1D2B in HeLa cells suggested a role in EGF receptor endocytosis and decreased cell viability of TBC1D2B-deficient HeLa cells upon serum deprivation. Genes encoding other TBC domain-containg GTPase-activating proteins, e.g. TBC1D7 and TBC1D20, TBC1D24 are associated with recessive neurodevelopmental disorders (with ID and/or seizures) and the pathophysiological defect in TBC1D2B-related disorder (deficit in vesicle trafficking and/or cell survival) is proposed to be similar to that of TBC1D24. Overall this gene can be considered for inclusion with amber/green rating in the ID panel and green in epilepsy panel. Sources: Literature |
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| Early onset or syndromic epilepsy v1.191 | TBC1D24 | Rebecca Foulger Source Wessex and West Midlands GLH was added to TBC1D24. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.190 | TBC1D24 | Rebecca Foulger Source NHS GMS was added to TBC1D24. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.189 | TBC1D24 | Rebecca Foulger reviewed gene: TBC1D24: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.188 | TBC1D24 | Tracy Lester reviewed gene: TBC1D24: Rating: GREEN; Mode of pathogenicity: ; Publications: 27281533; Phenotypes: Deafness , 614617, Deafness, 616044, DOORS syndrome 220500, Epileptic encephalopathy, early infantile, 615338, Myoclonic epilepsy, infantile, familial 605021; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy | TBC1D24 | Sarah Leigh commented on TBC1D24 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy | TBC1D24 | Sarah Leigh classified TBC1D24 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy | TBC1D24 | Sarah Leigh Added gene to panel | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||