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Intellectual disability syndromic and non-syndromic v2.104 RLF chirag patel Marked gene: RLF as ready
Intellectual disability syndromic and non-syndromic v2.104 RLF chirag patel Gene: rlf has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v2.104 RLF chirag patel Classified gene: RLF as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v2.104 RLF chirag patel Gene: rlf has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v2.103 RLF chirag patel gene: RLF was added
gene: RLF was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: RLF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: RLF were set to Neurodevelopmental disorder, MONDO:0700092, RLF-related
Review for gene: RLF was set to AMBER
Added comment: ESHG 2026

22 unrelated individuals with rare heterozygous de novo variants (14 frameshift, 8 nonsense) located in the last exon of RLF gene. Individuals presented with developmental delay, intellectual disability, autism-type behaviour, and Kabuki syndrome-like facial features.

RLF is a poly-ZNF protein which acts as a transcription factor. In vitro assays showed the variants profoundly altered the epigenome, the transcriptome and the DNA secondary structure. ONT whole genome sequencing in patient IPSCs showed hypermethylation and hypo-5-hydroxymethylation at multiple CpG sites. ATAC-seq demonstrated altered chromatin accessibility at promoters and enhancers in patient IPSCs. RNA-seq unveiled several differentially expressed genes enriched for disease-relevant gene ontology terms. RLP variants upregulated neuronal differentiation genes. RLF-ChIP-seq data showed a marked reduction in G4 access signal in patient iPSCs. Methylation arrays revealed a distinct methylation profile overlapping with Kabuki syndrome.
Sources: Other
Intellectual disability syndromic and non-syndromic v0.60 CRLF1 Zornitza Stark Marked gene: CRLF1 as ready
Intellectual disability syndromic and non-syndromic v0.60 CRLF1 Zornitza Stark Gene: crlf1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.60 CRLF1 Zornitza Stark Phenotypes for gene: CRLF1 were changed from to Cold-induced sweating syndrome 1, MIM#272430
Intellectual disability syndromic and non-syndromic v0.59 CRLF1 Zornitza Stark Mode of inheritance for gene: CRLF1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.58 CRLF1 Zornitza Stark Classified gene: CRLF1 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.58 CRLF1 Zornitza Stark Gene: crlf1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.57 CRLF1 Zornitza Stark reviewed gene: CRLF1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Cold-induced sweating syndrome 1, MIM#272430; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.0 CRLF1 Zornitza Stark gene: CRLF1 was added
gene: CRLF1 was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert Review Green,Genetic Health Queensland
Mode of inheritance for gene: CRLF1 was set to Unknown