| Date | Panel | Item | Activity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Repeat Disorders v1.6 | CSNK1E_FRA22A_CGG | Bryony Thompson Marked STR: CSNK1E_FRA22A_CGG as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Repeat Disorders v1.6 | CSNK1E_FRA22A_CGG | Bryony Thompson Str: csnk1e_fra22a_cgg has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Repeat Disorders v1.6 | CSNK1E_FRA22A_CGG | Bryony Thompson Classified STR: CSNK1E_FRA22A_CGG as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Repeat Disorders v1.6 | CSNK1E_FRA22A_CGG | Bryony Thompson Str: csnk1e_fra22a_cgg has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Repeat Disorders v1.5 | CSNK1E_FRA22A_CGG |
Bryony Thompson STR: CSNK1E_FRA22A_CGG was added STR: CSNK1E_FRA22A_CGG was added to Repeat Disorders. Sources: Literature Mode of inheritance for STR: CSNK1E_FRA22A_CGG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for STR: CSNK1E_FRA22A_CGG were set to 40751262; 39107278 Phenotypes for STR: CSNK1E_FRA22A_CGG were set to CSNK1E-related progressive myoclonic epilepsy and developmental and epileptic encephalopathy Review for STR: CSNK1E_FRA22A_CGG was set to AMBER Added comment: PMID 39107278 and 40751262 report 4 unrelated families with a heterozygous CGG expansion in the 5'UTR of CSNK1E at fragile site FRA22A. 3 probands had developmental and epileptic encephalopathy and 1 had progressive myoclonic epilepsy from age 10. Analysis of 1000 Genomes ONT data (n=908) suggests a normal range up to 48 repeats (98.7% <20). Neither paper proposes a pathogenic threshold. The affected proband had 745 repeats, her unaffected 18-year-old sister 980 and their unaffected mother 131. An affected DEE proband had ~430-700 repeats and an unaffected carrier mother ~500. Hypermethylation with ~50% reduced expression in fibroblasts is suggested to be the mechanism. The same hypermethylation was found in 6/23,116 controls. Further probands/families are required to confirm the gene-disease association. Comment on list classification: Unaffected carriers occur throughout the expansion range and no pathogenic threshold exists, and not useful in the clinical diagnostic setting. Sources: Literature |
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