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| Intellectual disability syndromic and non-syndromic v0.5236 | POU3F2 | Ain Roesley Classified gene: POU3F2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.5236 | POU3F2 | Ain Roesley Gene: pou3f2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.5238 | POU3F2 | Ain Roesley Phenotypes for gene: POU3F2 were changed from Autism spectrum disorder, NDD, and adolescent-onset obesity; neurodevelopmental disorder MONDO:0700092, POU3F2-related to Autism spectrum disorder, NDD, and adolescent-onset obesity; neurodevelopmental disorder MONDO:0700092, POU3F2-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.5237 | POU3F2 | Ain Roesley Phenotypes for gene: POU3F2 were changed from Autism spectrum disorder, NDD, and adolescent-onset obesity; neurodevelopmental disorder MONDO:0700092, POU3F2-related to Autism spectrum disorder, NDD, and adolescent-onset obesity; neurodevelopmental disorder MONDO:0700092, POU3F2-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.5237 | POU3F2 | Ain Roesley Phenotypes for gene: POU3F2 were changed from Autism spectrum disorder, NDD, and adolescent-onset obesity; neurodevelopmental disorder MONDO:0700092, POU3F2-related to Autism spectrum disorder, NDD, and adolescent-onset obesity; neurodevelopmental disorder MONDO:0700092, POU3F2-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.5237 | POU3F2 | Ain Roesley Phenotypes for gene: POU3F2 were changed from Autism spectrum disorder, NDD, and adolescent-onset obesity to Autism spectrum disorder, NDD, and adolescent-onset obesity; neurodevelopmental disorder MONDO:0700092, POU3F2-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.5235 | POU3F2 | Ain Roesley Classified gene: POU3F2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.5235 | POU3F2 | Ain Roesley Gene: pou3f2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.5236 | POU3F2 | Ain Roesley Marked gene: POU3F2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.5236 | POU3F2 | Ain Roesley Gene: pou3f2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.5236 | POU3F2 | Ain Roesley Classified gene: POU3F2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.5236 | POU3F2 | Ain Roesley Gene: pou3f2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.5234 | POU3F2 | Sarah Pantaleo commented on gene: POU3F2: Both loss of function and gain of function demonstrated | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.5234 | POU3F2 |
Sarah Pantaleo gene: POU3F2 was added gene: POU3F2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature Mode of inheritance for gene: POU3F2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: POU3F2 were set to PMID: 37207645 Phenotypes for gene: POU3F2 were set to Autism spectrum disorder, NDD, and adolescent-onset obesity Penetrance for gene: POU3F2 were set to unknown Mode of pathogenicity for gene: POU3F2 was set to Other Review for gene: POU3F2 was set to GREEN Added comment: We associate ultra-rare variants in POU3F2, encoding a central nervous system transcription factor, with syndromic obesity and neurodevelopment delay in 12 individuals. Demonstrate variant pathogenicity through in vitro analysis. Used exome sequencing, GeneMatcher and Genomics England 100,000 Genomes Project rare disease database. Both truncating and missense variants in over 10 individuals sharing autism spectrum disorder, NDD, and adolescent-onset obesity (may have had other features eg. CAKUT in 2 individuals, diabetes in two) . Affected individuals presented with low-to-normal birth weight and infantile feeding difficulties but developed insulin resistance and hyperplasia during childhood. With the exception of an early truncating variant, the variants showed adequate nuclear translocation but overall disturbed DNA-binding ability and promoter activation. Variants absent from population and clinical databases. Almost all constituted putatively non-inherited de novo variants (8/10). Functional studies provide evidence for loss of function in eight and gain of function in one obesity-associated POU3F2 variant. One variant did not impact POU3F2-promoter activation, leaving the possibility for further path-mechanisms. Sources: Literature |
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