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| Intellectual disability - microarray and sequencing v2.645 | ODC1 | Eleanor Williams Classified gene: ODC1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v2.645 | ODC1 | Eleanor Williams Added comment: Comment on list classification: Changing rating from grey to green. 5 unrelated cases with likely disease causing variants. All de novo. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v2.645 | ODC1 | Eleanor Williams Gene: odc1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v2.644 | ODC1 | Eleanor Williams commented on gene: ODC1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v2.558 | ODC1 |
Konstantinos Varvagiannis gene: ODC1 was added gene: ODC1 was added to Intellectual disability. Sources: Literature,Expert Review Mode of inheritance for gene: ODC1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: ODC1 were set to 30239107; 30475435 Phenotypes for gene: ODC1 were set to Global developmental delay; Intellectual disability; Macrocephaly; Alopecia; Ectodermal dysplasia Penetrance for gene: ODC1 were set to unknown Review for gene: ODC1 was set to GREEN Added comment: PMIDs 30239107 and 30475435 report on 5 cases of de novo truncating ODC1 variants in unrelated families. One concerned a stillborn male. The 4 remaining individuals presented with a similar phenotype consisting of alopecia and other ectodermal anomalies, DD/ID, relative or absolute macrocephaly and common facial features. DD/ID was severe in some instances and many of these individuals had extensive prior testing for other disorders (Fragile-X, PTEN, SLC2A1, chromosomal disorders, etc). ODC1 (ornithine decarboxylase 1) converts enzymatically ornithine to putrescine. All variants reported to date are truncating but lead to gain-of-function. Specifically they affect a 37 amino acid c-terminal destabilization region critical for the degradation of ODC1 and - as a result - lead to increased levels of ODC1 as well as putrescine. A mouse model with identical phenotype has been described several years ago. The role of ODC inhibitors is extensively discussed in both publications. As a result, ODC1 can be considered for inclusion in the ID panel as green (or amber). Sources: Literature, Expert Review |
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