IBMDx study

Gene: RPL9

I don't know

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.

Created: 30 Sep 2020, 8:35 p.m. | Last Modified: 30 Sep 2020, 8:35 p.m.

Panel Version: 0.165

PMID: 29114930, de novo splice site variant, c.-2+1G>C, functional impact of this variant is likely deleterious but not proven. Inherited missense variant reported in PMID 20116044, p.Arg125Ser is present in 31 hets in gnomad.
Sources: Expert list

Created: 14 Sep 2020, 8:40 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Diamond Blackfan anaemia

Publications

• 29114930
• 20116044
• 31799629