| Date | Panel | Item | Activity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Mendeliome v1.2666 | PDCD2 | Zornitza Stark Marked gene: PDCD2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.2666 | PDCD2 | Zornitza Stark Gene: pdcd2 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.2666 | PDCD2 | Zornitza Stark Classified gene: PDCD2 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.2666 | PDCD2 | Zornitza Stark Gene: pdcd2 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.2665 | PDCD2 |
Zornitza Stark gene: PDCD2 was added gene: PDCD2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PDCD2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PDCD2 were set to 40208938 Phenotypes for gene: PDCD2 were set to Non-immune hydrops fetalis, MONDO:0009369, PDCD2-related Review for gene: PDCD2 was set to AMBER Added comment: PMID: 40208938- Novel biallelic PDCD2 variants associated with hydrops fetalis and early pregnancy loss in two affected families. Family 1 with RPL had three fetuses with NIHF who were all homozygous for p.(Pro28Ser) in PDCD2, while Family 2 had p.(Pro28Ser) in trans with p.(Arg34Pro) in two fetuses with NIHF. Family 2 was additionally notable for having a healthy child who was homozygous for the reference allele, consistent with appropriate disease segregation with the PDCD2 variants. Functional studies using primary fetal fibroblasts and human cell lines for both variants showed reduced PDCD2 mRNA level in affected patients' fibroblasts, reduced cellular accumulation of mutant proteins with impaired ability to associate with the 40S subunit ribosomal protein uS5, and further depletion of PDCD2 in fibroblast cells severely impacted ribosome biogenesis. It is notable that formation of the PDCD2-uS5 complex was not completely abolished by the patient variants and that rRNA processing was only partially impaired, as indicated by levels of 40S pre-rRNAs. We thus suspect that the PDCD2 pathogenic variants p.(Pro28Ser) and p.(Arg34Pro) are hypomorphic alleles, with a low level of residual function allowing for cellular differentiation and growth to a certain extent. Sources: Literature |
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