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Intellectual disability - microarray and sequencing v4.53 | FBXO28 |
Arina Puzriakova Tag Q3_22_rating was removed from gene: FBXO28. Tag Q3_22_MOI was removed from gene: FBXO28. |
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Intellectual disability - microarray and sequencing v4.53 | FBXO28 | Arina Puzriakova reviewed gene: FBXO28: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intellectual disability - microarray and sequencing v4.52 | FBXO28 |
Arina Puzriakova Source NHS GMS was added to FBXO28. Source Expert Review Green was added to FBXO28. Rating Changed from Amber List (moderate evidence) to Green List (high evidence) |
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Intellectual disability - microarray and sequencing v3.1696 | FBXO28 | Sarah Leigh Phenotypes for gene: FBXO28 were changed from Developmental and epileptic encephalopathy 100 (# 619777) to Developmental and epileptic encephalopathy 100, OMIM:619777; developmental and epileptic encephalopathy 100, MONDO:0030695 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intellectual disability - microarray and sequencing v3.1695 | FBXO28 | Sarah Leigh edited their review of gene: FBXO28: Added comment: Associated with relevant phenotype in OMIM and as definitive Gen2Phen gene. At least six variants have been reported in at least six cases. In one of these cases the variant was inherited from the unanaffected mother, who was mosaic (PMID: 33280099), otherwise the variants were de novo heterozygotes (PMIDs: 30160831; 33280099).; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intellectual disability - microarray and sequencing v3.1695 | FBXO28 |
Sarah Leigh Tag Q3_22_rating tag was added to gene: FBXO28. Tag Q3_22_MOI tag was added to gene: FBXO28. |
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Intellectual disability - microarray and sequencing v3.1695 | FBXO28 | Sarah Leigh Classified gene: FBXO28 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intellectual disability - microarray and sequencing v3.1695 | FBXO28 | Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intellectual disability - microarray and sequencing v3.1695 | FBXO28 | Sarah Leigh Gene: fbxo28 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intellectual disability - microarray and sequencing v3.1561 | FBXO28 |
Konstantinos Varvagiannis gene: FBXO28 was added gene: FBXO28 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: FBXO28 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: FBXO28 were set to 30160831; 33280099 Phenotypes for gene: FBXO28 were set to Developmental and epileptic encephalopathy 100 (# 619777) Penetrance for gene: FBXO28 were set to unknown Review for gene: FBXO28 was set to GREEN Added comment: Heterozygous pathogenic FBXO28 variants cause Developmental and epileptic encephalopathy 100 (# 619777). At least 10 individuals with monoallelic missense / truncating FBXO28 variants have been reported. The subject with de novo frameshift variant initially reported by Balak et al (2018 - PMID:30160831) was included with additional clinical details in a recent report along with 9 further individuals (Schneider et al, 2021 - PMID: 33280099). The phenotype corresponds to a developmental and epileptic encephalopathy with severe/profound ID. As discussed by Schneider et al, all individuals had DD prior to seizure onset which occurred at a median age of 22.5 months (range: 8m - 5y). The authors noted that missense variants may be associated with a milder phenotype (e.g. seizures occurred at the age of 4-5 years in 3 individuals). Given these, FBXO28 appears to be relevant for inclusion in the current panel, with investigations prior to seizure onset. As in the summary by Schneider et al, the gene encodes F-box only protein 28, a ubiquitin ligase promoting ubiquitination and degradation of phosphorylated proteins. While FBXO28 has been suggested to have a critical role in 1q41q42 deletions (most spanning also WDR26) the authors note that a mechanism different than haploinsufficiency may underly FBXO28 encephalopathy. Importantly, all 5 truncating variants reported (and 2/4 missense ones) occurred in the last exon, making these variants less susceptible to NMD. 2 other (of the 4) missense variants clustered in the F-box domain, which the authors hypothesize may correspond to a second pathogenic region. 7/9 variants arose de novo while 2 individuals had inherited a missense and a stopgain variant from mosaic unaffected parents (2.5% and 6%). A comparison of the FBXO28-associated phenotype with the respective of 1q41q42 deletions and WDR26-related NDD is also made. Consider inclusion in the ID panel with green (or amber) rating. Please consider inclusion in other possibly relevant panels (e.g. microcephaly (4/10), movement disorders, etc). Sources: Literature |