Expression profile of FSHD supports a link between retinal vasculopathy and muscular dystrophy
Bibliographic record
Abstract
BACKGROUND: Facioscapulohumeral muscular dystrophy (FSHD) is caused by deletions within a tandem array of D4Z4 repeats on chromosome 4q35. In addition to muscle degeneration, most patients with FSHD develop abnormalities of the retinal vasculature. Previous work has suggested that muscle degeneration in FSHD results from increased expression of genes proximal to the deletion, including FRG1. OBJECTIVES: To reexamine this mechanism and identify pathways that are abnormally regulated early in the disease process. METHODS: We prospectively studied gene expression in skeletal muscle in patients with FSHD (n = 19) vs healthy individuals (n = 30) and patients with myotonic dystrophy type 1 (n = 12). We used oligonucleotide microarrays for global analysis of gene expression and reverse transcriptase-PCR (RT-PCR) to assess expression or alternative splicing for particular genes. RESULTS: Expression of FRG1 was not increased in patients with FSHD, either by microarray analysis or quantitative RT-PCR. Among genes on 4q35, only LRP2BP showed upregulation that was specific to FSHD. However, neither LRP2BP nor FRG1 showed imbalance of allelic expression by RT-PCR. After filtering out genes that showed similar dysregulation in other forms of muscular dystrophy, only 44 genes were specifically upregulated early in FSHD. Among these, 34 genes were characterized or partially characterized, of which 11 (32%) had a role in vascular smooth muscle or endothelial cells. CONCLUSION: Expression of genes on chromosome 4q35 was normally regulated in the early stages of facioscapulohumeral muscular dystrophy. Our results support a possible link between muscular dystrophy and retinal vasculopathy in facioscapulohumeral muscular dystrophy.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".