Development of simple and effective PCR based assay to detect PCCA mutation (c.425G > A) among Saudi carriers and functional study of the homozygous PCCA mutations
Bibliographic record
Abstract
The aim of this study is to develop a rapid and effective method to screen for Saudi carriers of one of the most common propionic acidemia mutations (c.425G > A) and to study the functional impact of this mutation. Using allele-specific primers, we have developed a qPCR assay that clearly distinguishes heterozygotes from mutated and wild type homozygotes that overcome the dependence on labor-intensive gene sequencing. We show here that (i) qPCR rapid test has strong accuracy in detecting (c.425G > A) mutation in heterozygotes and homozygotes individuals and that the Ct-value cut-offs were estimated to be and 23.37 ± 0.04 (CV-6 %, 95 %CI-7.25) for homozygote, 25.06 ± 0.02 (CV-3.5 %, 95 %CI-7.85) for heterozygote PCCA c.425G > A mutation and 29.55 ± 0.002 (CV-11 %, 95 %CI-1.41) for PCCA wild type; (ii) the incidence of PA heterozygotes/carriers in Saudi population is about 550/100,000; (iii) skin fibroblast assays show that homozygote c.425G > A mutation induced propionyl-CoA carboxylase activity abrogation, (iv) PA patients showed an increased level of propionyl carnitine C3 in blood and 3-hydroxy propionic acid and methyl citrate in urine. Conclusion: qPCR represent an effective strategy to assess for PCCA mutation carriers in the Saudi population and we believe that will help in preventing homozygosity in the population after been implemented in pre-marriage screening program.
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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 | 0.001 | 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".