ArticleGenetics in medicine : official journal of the American College of Medical Genetics2023
Clinical and functional heterogeneity associated with the disruption of retinoic acid receptor beta.
Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
7 citing papers in PubMed, 9 citations in OpenAlex.
- Whole-genome resequencing with multidimensional annotation revealed pathogenic networks in sirenomelia.Italian journal of pediatrics · 2026Article
- Impaired retinoic acid receptor-γ signaling underlies a heritable form of urothelial keratinizing squamous metaplasia.HGG advances · 2026Article
- Clinical features of syndromic microphthalmia in two novel RARB variants.Human genome variation · 2026Article
- The RaDiCo information system for rare disease cohorts.Orphanet journal of rare diseases · 2025Article
- GREGoR: Accelerating Genomics for Rare Diseases.ArXiv · 2024Article
- AHuman mutation · 2024Article
- Functional genomics and small molecules in mitochondrial neurodevelopmental disorders.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
55 authors at 20 institutions in 9 countries.
Funding
Abstract
purposeDominant variants in the retinoic acid receptor beta (RARB) gene underlie a syndromic form of microphthalmia, known as MCOPS12, which is associated with other birth anomalies and global developmental delay with spasticity and/or dystonia. Here, we report 25 affected individuals with 17 novel pathogenic or likely pathogenic variants in RARB. This study aims to characterize the functional impact of these variants and describe the clinical spectrum of MCOPS12.
methodsWe used in vitro transcriptional assays and in silico structural analysis to assess the functional relevance of RARB variants in affecting the normal response to retinoids.
resultsWe found that all RARB variants tested in our assays exhibited either a gain-of-function or a loss-of-function activity. Loss-of-function variants disrupted RARB function through a dominant-negative effect, possibly by disrupting ligand binding and/or coactivators' recruitment. By reviewing clinical data from 52 affected individuals, we found that disruption of RARB is associated with a more variable phenotype than initially suspected, with the absence in some individuals of cardinal features of MCOPS12, such as developmental eye anomaly or motor impairment.
conclusionOur study indicates that pathogenic variants in RARB are functionally heterogeneous and associated with extensive clinical heterogeneity.
Indexed as
Identifiers
What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.