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Intellectual disability

Gene: ODC1

Green List (high evidence)

ODC1 (ornithine decarboxylase 1)
EnsemblGeneIds (GRCh38): ENSG00000115758
EnsemblGeneIds (GRCh37): ENSG00000115758
OMIM: 165640, Gene2Phenotype
ODC1 is in 4 panels

2 reviews

Eleanor Williams (Genomics England Curator)

Comment on list classification: Changing rating from grey to green. 5 unrelated cases with likely disease causing variants. All de novo. Variants cause a gain-of-function.
Created: 14 Feb 2019, 2:46 p.m.
PMID: 30239107 (Bupp et al 2018) - 1 patient with heterozygous de novo nonsense mutation in the ODC1 gene (c.1342 A>T) identified by whole exome sequencing. Phenotypic manifestations include macrosomia, macrocephaly, developmental delay, alopecia, spasticity, hypotonia, cutaneous vascular malformation, delayed visual maturation, and sensorineural hearing loss. Red blood cells from the patient showed elevated ODC protein and polyamine levels compared to healthy controls indicating that this is a gain-of-function variant.

PMID: 30475435 (Rodan et al 2018) - 4 patients (1 stillborn) with a distinct neurometabolic disorder associated with de novo heterozygous, gain-of-function variants in the ODC1 gene. 4 different variants found. This disorder presents with global developmental delay, ectodermal abnormalities including alopecia, absolute or relative macrocephaly, and characteristic facial dysmorphisms. No epilepsy observed. None of the reported variants are found in the Broad. gnomAD database. The variants are predicted to have a gain-of-function effect as the mutant protein escapes nonsense‐mediated decay (NMD) and has reduced degradation compared to wild‐type.
Created: 14 Feb 2019, 2:44 p.m.

Konstantinos Varvagiannis (Other)

Green List (high evidence)

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.

Thus, ODC1 can be considered for inclusion in the ID panel as green (or amber).
Sources: Literature, Expert Review
Created: 29 Nov 2018, 1:01 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Global developmental delay; Intellectual disability; Macrocephaly; Alopecia; Ectodermal dysplasia



Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
  • Expert Review Green
  • Global developmental delay
  • Intellectual disability
  • Macrocephaly
  • Alopecia
  • Ectodermal dysplasia
Clinvar variants
Variants in ODC1
Panels with this gene

History Filter Activity

14 Feb 2019, Gel status: 3

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: odc1 has been classified as Green List (High Evidence).

29 Nov 2018, Gel status: 0

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes, Set penetrance

Konstantinos Varvagiannis (Other)

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