Reporting a Homozygous Case of Neurodevelopmental Disorder Associated With a Novel <scp><i>PRPF8</i></scp> Variant
Bibliographic record
Abstract
BACKGROUND: While recently identified heterozygous PRPF8 variants have been linked to various human diseases, their role in neurodevelopmental disorders (NDDs) remains ambiguous. This study investigates the potential association between homozygous PRPF8 variants and NDDs. Most PRPF8 variants are primarily associated with retinal diseases; however, we analyze a family with multiple members diagnosed with NDDs. METHODS: Using exome sequencing (ES), the cause of behavioral problems and intellectual disabilities (IDs) of two sisters from a consanguineous parents was solved, and the results confirmed by direct sanger sequencing method likewise protein modeling to assess the structural impact of the identified variant on the PRPF8 protein has been done. RESULTS: ES identified a novel homozygous variant, PRPF8 c.257G>T, p.R86M. To the best of our knowledge at the time of writing this manuscript, the mentioned variant has not been reported in relation to NDDs. Protein modeling provided another line of evidence proving the pathogenicity of the novel variant. CONCLUSION: Our findings indicate that the p.R86M variant may disrupt normal protein function by changing its structure and probably its interaction, potentially leading to the observed neurodevelopmental phenotypes. This study highlights the first link between the PRPF8 variant and NDDs, suggesting a distinct role for specific PRPF8 variants in the etiology of NDDs. These results warrant further investigation into the mechanisms by which PRPF8 variants contribute to NDDs, emphasizing the need for comprehensive genetic screening in families with unexplained neurodevelopmental conditions.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.003 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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 source (direct Gemma or distilled Codex), 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".