FRA12A_DIP2B-criTRia#469
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| "Inheritance": "AD", | ||
| "Curator": "Gabriel Zinser", | ||
| "Date": "05/20/2026", | ||
| "Description": "Intellectual developmental disorder, FRA12A type. Impaired intellectual development with or without other anomalies has been described in patients with over 40% of cells expressing FRA12A [@omim:136630].", |
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We've been using this description box to summarize the evidence reported below, but this description would be very good for the locus page! Here's an idea that's more consistent with other loci criTRia pages: "9 patients have been studied with intellectual developmental disorder, all showing inheritance and functional evidence. PMID: 39854091 found that higher rate of methylation affects phenotype. Regulatory impact and functional alteration in cardiac tissue were also found."
| "Evidence type": "Allele", | ||
| "Score": 2.0, | ||
| "Citation": "pmid:39854091", | ||
| "Evidence detail": "larger methylated expansions linked to intellectual disability while smaller unmethylated alleles linked to movement disorder phenotype. Finds pathogenic range.", |
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Larger expansion causes affects phenotype or rate of methylation?
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Both. Larger expansions have higher methylation and are more commonly associated with intellectual disorder while smaller expansions have lower methylation and are more associated with movement disorder
| "experimental_evidence_details": [ | ||
| { | ||
| "Evidence type": "Regulatory impact", | ||
| "Score": 2.0, |
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I'd give this a 1.5, 0.5 each for methylation, underexpression, and overexpression. In my mind the loss of activity, loss of regulatory activity and silencing are mechanisms. If you disagree though I'd be happy to make this a conversation
| }, | ||
| { | ||
| "Evidence type": "Patient cells", | ||
| "Score": 2.0, |
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1.0, probably. This sounds like it's one experiment with two findings
Updated the description and evidence details for the FRA12A_DIP2B locus, including new scores, citations, and publication dates.
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I went through a few of the papers and added some extra detail to the descriptions. The main reason that I did this is that I was pretty surprised this is scoring so high, so I was looking for any inconsistency in the evidence. What I noticed is that there is quite a range of phenotypes mentioned. Intellectual disability, ataxia/movement disorder, epilepsy, and even cardiovascular disease (which may not be relevant but isn't score driving, so not concerning).
If we lump the ID/ataxia/epilepsy phenotypes and treat them as a phenotypic spectrum, then the score is reasonable. If we break them out, we might get a different answer. So we should probably be quite explicit about this.
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I reread the pmid:39854091 study cited for evidence that allele size is associated with different phenotypes. I realize this is actually only in the discussion and they're talking about FMR1, not DIP2B. They didn't find this (it's not in the results); they are just hypothesizing that DIP2B could be like FMR1 and show a similar pattern. So I removed allele evidence, and this might need to be removed or at least described as a hypothesis on the locus page. |
…ce that is cardiac related
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I also reduced the score for PMID: 37248219 to 1.0 (0.5 + 0.5) because while there are multiple findings, there are just two experiments. |
…resulting in Moderate.
3 participants
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