Įgimtos antinksčių hiperplazijos, dėl 21-hidroksilazės trūkumo, genotipo ir fenotipo sąsaja
Bibliographic record
Abstract
Author: Aida Dawit Ghirmatsion Title: Correlation of genotype-phenotype of congenital adrenal hyperplasia due to 21-hydroxylase deficiency Aim: To perform a systematic review of the database related to the correlation between genotype of 21-hydroxylase deficiency (due to CYP21A2 gene mutation) and form of CAH (Congenital Adrenal Hyperplasia). Objectives: 1. To select all available publications in databases, related to 21-OHD genotype and phenotype correlation. 2. To assess the prevalence of the most frequent mutations of CYP21A2 gene in populations. 3. To apply model of PRISMA systematic review for performing the study. Methodology: The publications for the systematic review were found using NCBI PubMed database. The 195 references were found and assessed for the review. Ten references were selected for the detailed analysis after inclusion and exclusion criteria. The risk of bias of the studies was assessed using Newcastle-Ottawa Scale for observational studies. Results: In total, 10 articles were selected for analysis of genotype-phenotype correlation of the rare disease congenital adrenal hyperplasia and the prevalence of CYP21A2 gene pathogenic mutations from different cohorts. The review assessed the correlation of the groups of genotypes (Null, A, B, C) with the three forms (salt-wasting, simple virilizing, non-classical) of CAH due to 21-OHD. It presented a better genotype-phenotype correlation in the severe salt wasting form than the milder forms. Almost all the publications presented the highest correlation of genotype-phenotype in genotype Null (determine <1 % residual 21-OH activity) followed by genotype A (determine ~1% 21-OH activity). Inconsistent results were also present which suggests that there is discordance of genotype-phenotype correlation. The frequency of I2G and deletion/conversions mutation of CYP21A2 gene were also the highest in most publications. Discussion: Correlation of genotype-phenotype were analyzed in the results which presented good correlation and discordance in some cases. It is also described the severe form SW had the best correlation in most cohorts’ studies. In most cases the explanation for inconsistent results of discordance of genotype –phenotype correlation was unknown. I2G and deletions/conversions were found to be most frequent in the cohort studies taken for the review while I172N for SV phenotype and V281L for non-classic phenotype. Conclusion: Analysis of genotype-phenotype correlation shows a good correlation in severe CAH forms and discordance in mild CAH forms. In most cases the explanation for inconsistent results of discordance of genotype-phenotype correlation was unknown. Although the most frequent mutations were assessed in different countries, still, there is a deficiency of data about genotype-phenotype correlation in most populations. The knowledge of a correlation between genotype and phenotype could help to prescribe the dose of the most appropriate glucocorticoids (GC) for treatment, predict and prevent complications related to CAH and long-term treatment of GC.
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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 | 0.002 | 0.009 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.004 | 0.004 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.008 | 0.001 |
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".