Activity
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| Neonatal diabetes v5.11 | RNU6ATAC |
Ida Ertmanska changed review comment from: MedRxiv preprint Johnson et al., 2025 doi: https://doi.org/10.1101/2025.09.12.25335567 identified 19 individuals with early-onset diabetes (diagnosed <5 years) and additional clinical features who had biallelic pathogenic variants in the novel disease gene RNU6ATAC (n=7) or in RNU4ATAC (n=12). 12/19 had additional immune features of immune dysregulation. Around 60% of patients also had microcephaly and developmental delay. Among the 4 families with biallelic RNU4ATAC variants, the variants reported were: n.4T>C, n.6G>A, n.43G>A, n.68C>A, n.71C>T (homozygous or compound het). RNU6ATAC has not yet been linked to any phenotypes in OMIM (accessed 29th Dec 2025).; to: MedRxiv preprint Johnson et al., 2025 doi: https://doi.org/10.1101/2025.09.12.25335567 identified 19 individuals with early-onset diabetes (diagnosed <5 years) and additional clinical features who had biallelic pathogenic variants in the novel disease gene RNU6ATAC (n=7) or in RNU4ATAC (n=12). 12/19 had additional immune features of immune dysregulation. Around 60% of patients also had microcephaly and developmental delay. Among the 4 families with biallelic RNU6ATAC variants, the variants reported were: n.4T>C, n.6G>A, n.43G>A, n.68C>A, n.71C>T (homozygous or compound het). RNU6ATAC has not yet been linked to any phenotypes in OMIM (accessed 29th Dec 2025). |
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| Neonatal diabetes v5.11 | RNU4ATAC | Ida Ertmanska Tag locus-type-rna-small-nuclear tag was added to gene: RNU4ATAC. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Neonatal diabetes v5.11 | RNU4ATAC | Ida Ertmanska Phenotypes for gene: RNU4ATAC were changed from neonatal diabetes; developmental delay; microcephaly; skeletal abnormalities; hypothyroidism; humoral immune defect; hepatic disorder; growth failure; failure to thrive; atopic dermatitis to RNU4ATAC spectrum disorder, MONDO:0100558; neonatal diabetes; developmental delay; microcephaly; skeletal abnormalities; hypothyroidism; humoral immune defect; hepatic disorder; growth failure; failure to thrive; atopic dermatitis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Neonatal diabetes v5.10 | RNU4ATAC | Ida Ertmanska Classified gene: RNU4ATAC as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Neonatal diabetes v5.10 | RNU4ATAC | Ida Ertmanska Gene: rnu4atac has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Neonatal diabetes v5.9 | RNU4ATAC | Ida Ertmanska commented on gene: RNU4ATAC: Comment on list classification: There are 12 unrelated individuals with biallelic RNU4ATAC variants and early-onset diabetes (article not yet peer-reviewed). Hence, this gene will be recommended for promotion to Green on Neonatal diabetes panel once the article is published. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Neonatal diabetes v5.9 | RNU4ATAC | Ida Ertmanska reviewed gene: RNU4ATAC: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: RNU4ATAC spectrum disorder, MONDO:0100558; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Neonatal diabetes v5.9 | RNU4ATAC |
Anna-Marie Johnson gene: RNU4ATAC was added gene: RNU4ATAC was added to Neonatal diabetes. Sources: Literature Mode of inheritance for gene: RNU4ATAC was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RNU4ATAC were set to MedRxiv preprint Johnson et al., 2025 doi: https://doi.org/10.1101/2025.09.12.25335567 Phenotypes for gene: RNU4ATAC were set to neonatal diabetes; developmental delay; microcephaly; skeletal abnormalities; hypothyroidism; humoral immune defect; hepatic disorder; growth failure; failure to thrive; atopic dermatitis Penetrance for gene: RNU4ATAC were set to Complete Mode of pathogenicity for gene: RNU4ATAC was set to Other Review for gene: RNU4ATAC was set to GREEN Added comment: RNU4ATAC is a non-protein-coding gene and a component of the minor spliceosome, a protein-RNA complex mediating splicing of ~700 genes containing U12/minor-type introns. Johnson et al report RNU4ATAC as a novel disease gene causing monogenic autoimmune diabetes (median onset: 20 weeks) with additional immune dysregulation; whole genome sequencing of 7 unrelated individuals identified homozygous or compound heterozygous variants in RNU4ATAC, all known causes of monogenic diabetes had already been excluded. Sanger sequencing of the RNU4ATAC gene in patients with neonatal diabetes of unknown cause identified a further 5 unrelated individuals with biallelic variants in RNU4ATAC. RNA-seq from 3 unrelated individuals confirmed intron retention in comparison to controls. Multi-omic analysis of patient samples revealed a profound B cell developmental defect. This is the first report of pathogenic variants in non-coding genes causing monogenic diabetes, and also extends the phenotype of RNU4ATACopathies. Sources: Literature |
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