X-linked hypophosphatemia caused by a deep intronic variant in PHEX identified by PCR-based RNA analysis of urine-derived cells
Bibliographic record
Abstract
X-linked hypophosphatemia (XLH) is caused by dominant inactivating mutations in the phosphate regulating endopeptidase homology, X-linked (PHEX), resulting in elevated fibroblast growth factor 23 (FGF23), hypophosphatemia, rickets and osteomalacia. PHEX variants are identified in approximately 85 % of individuals with XLH, which leaves a substantial proportion of patients with negative DNA-based genetic testing. Here we describe a 16-year-old male who had typical features of XLH on clinical and radiological examination. Genomic DNA sequencing of a hypophosphatemia gene panel did not reveal a pathogenic variant. We therefore obtained a urine sample, established cell cultures and obtained PHEX cDNA from urine-derived cells. Sequencing of exon-spanning PCR products demonstrated the presence of an 84 bp pseudoexon in PHEX intron 21 due to a deep intronic variant (c.2147+1197A>G), which created a new splice donor site in intron 21. The corresponding PHEX protein would lack 33 amino acids on the C-terminus and instead include an unrelated sequence of 17 amino acids. The patient and his affected mother both had this variant. This report highlights that individuals with the typical clinical characteristics of XLH and negative genomic DNA sequence analysis can have deep intronic PHEX variants that are detectable by PCR-based RNA diagnostics.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.000 |
| 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 | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".