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| Bone Marrow Failure v0.165 | RPL9 |
Zornitza Stark edited their review of gene: RPL9: Added comment: New publication, second individual reported with same c.-2+1G>C variant in the 5′UTR of RPL9, deleterious effect demonstrated, functional data, upgrade to Amber: PMID: 31799629 (2020) - Female infant diagnosed with Diamond-Blackfan anaemia carrying a de novo variant (c.-2+1G>C) in the 5′UTR of RPL9, predicted to affect the donor splice site of exon 1. Phenotypic overlap can be seen with the previously reported case with the same variant, including colitis, thumb anomaly, and microcephaly. Functional studies showed the variant impairs processing of pre-rRNA during ribosome biogenesis, stabilises TP53 and impairs the proliferation and differentiation of erythroid cells. Zebrafish models of RPL9 LoF recapitulate the anaemia phenotype.; Changed rating: AMBER; Changed publications: 29114930, 20116044, 31799629 |
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| Bone Marrow Failure v0.56 | TP53 | Zornitza Stark Marked gene: TP53 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Bone Marrow Failure v0.56 | TP53 | Zornitza Stark Gene: tp53 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Bone Marrow Failure v0.56 | TP53 | Zornitza Stark Classified gene: TP53 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Bone Marrow Failure v0.56 | TP53 | Zornitza Stark Gene: tp53 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Bone Marrow Failure v0.55 | TP53 |
Zornitza Stark gene: TP53 was added gene: TP53 was added to Bone Marrow Failure. Sources: Expert list Mode of inheritance for gene: TP53 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: TP53 were set to 30146126; 24013501; 23770245 Phenotypes for gene: TP53 were set to Bone marrow failure syndrome 5, MIM# 618165 Mode of pathogenicity for gene: TP53 was set to Other Review for gene: TP53 was set to AMBER Added comment: Two unrelated individuals with de novo variants in this gene, both resulted in the same truncation of the protein with a loss of 32 residues from the C-terminal end (Ser362AlafsTer8). The deletion is postulated to compromise binding of negative transcriptional regulators, resulting in augmented p53 function, not loss of function. Mouse models with animals lacking the C-terminal end of Tp53 show similar abnormalities. Sources: Expert list |
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