Genetics of Leber congenital amaurosis
Bibliographic record
Abstract
Abstract Purpose To give an overview of our current knowledge of the genetic causes of Leber congenital amaurosis (LCA). Methods Current literature on the genetic causes of LCA and the function of the defective gene products will be reviewed. In addition therapeutic options for the various genetic subtypes will be discussed. Results Linkage analysis, homozygosity mapping and candidate gene analysis facilitated the identification of 15 genes mutated in patients with LCA, which together explain approximately 70% of the cases. Several of these genes have also been implicated in other non‐syndromic or syndromic retinal diseases, such as retinitis pigmentosa and Joubert syndrome, respectively. CEP290, GUCY2D and CRB1 are the most frequently mutated LCA genes; one intronic CEP290 mutation (p.Cys998X) is found in 20% of LCA patients from north‐western Europe, although this frequency is lower in other populations. The LCA genes encode proteins with a wide variety of retinal functions, such as photoreceptor morphogenesis, phototransduction, vitamin A cycling and intra‐photoreceptor ciliary transport processes. Rodent, avian and canine models for LCA have been successfully corrected employing adeno‐associated virus or lentivirus‐based gene therapy. Moreover, phase 1 clinical trials have been carried out in humans with RPE65 deficiencies. In addition, a phase 1 clinical trial with a retinoid compound has been initiated in LCA patients with RPE65 and LRAT mutations. Conclusion Future LCA research will focus on the identification of the remaining causal genes, the elucidation of the molecular mechanisms of disease in the retina, and the development of gene therapy approaches for different genetic subtypes of LCA.
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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".