Genomic imprinting

Gene: OOEP

I don't know

Comment on list classification: This gene is rated red on this panel after seeking clinical opinion from Helen Brittain.

This is a maternal effect gene with similar genotypes causing different phenotypes.

In PMID:29574422, a homozygous variant in mother resulted in a phenotype suggestive of MLID in the offspring, who was heterozygous for the same variant. The current standard testing for this type of finding appears to be MLID methylation test in the proband. In addition, this family is from South East Asian descent and this ethnicity is under-represented in population cohorts raising the question whether the variant might not be responsible for the clinical presentation.

In PMID:35946397, compound heterozygous variants (one of these variants is the same as the homozygous variant above) resulted in recurrent preimplantation embryonic arrest in the patient, which is a different phenotype from the one above. In addition, this phenotype does not clearly lead to inclusion in any current panels within the Genomic Medicine Service.

Created: 23 Jun 2025, 2:37 p.m. | Last Modified: 23 Jun 2025, 2:37 p.m.

Panel Version: 0.153

PMID:29574422 reported 15 pedigrees in which offspring had disturbance of imprinting. The mother from one of these pedigrees was identified with a homozygous 109C>T (p.Arg37Trp) variant in OOEP gene. The offspring had birth weight <0.4th centile, hyperglycaemia 1–3.5 months, pelvic renal dilatation and developmental delay. The imprinting defect (hypomethylation) noted in these loci via targeted testing: PLAGL1, IGF2R, DIRAS3, GRB10, SNRPN, IGF1R. This patient was included in the literature review in PMID:35296332.

PMID:35946397 reported 118 Chinese patients who experienced recurrent preimplantation embryonic arrest during assisted reproductive technology treatments. Whole‐exome sequencing of these patients resulted in the identification of compound heterozygous missense variants (c.110G>C (p.Arg37Pro) and c.109C>G (p.Arg37Gly)) in the OOEP gene in one of them. Functional studies of these variants in HEK 293T cells resulted in reduced expression of the protein. In addition, RNA-sequencing using abandoned embryos from controls and the patient with OOEP variants confirmed that these variants modestly affected zygotic genome activation.

It is noted by the authors that similar genotypes cause different phenotypes in the two different patients and hence the reason need to be further explored.

This gene has not been associated with any phenotypes in OMIM or Gene2Phenotype.

This gene has also been included in the guidelines for Multi-locus imprinting disturbance (MLID) in PMID:39090763.
Sources: Literature

Created: 20 Jun 2025, 3:18 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

• 29574422
• 35946397
• 39090763