Authors
Carlos F Panqueba Arias, Ingry K Rojas Rodriguez, Rossi I Quero, Cielo C Baez
Published in
Cureus. Volume 18. Issue 8. Pages e114812. Epub Aug 19, 2026.
Abstract
X-linked hypophosphatemic rickets (XLH) is the most common inherited cause of renal phosphate wasting. It is typically caused by pathogenic variants in the phosphate-regulating endopeptidase homolog, X-linked (PHEX gene), which lead to increased levels of fibroblast growth factor 23 (FGF23). However, noncanonical intronic variants represent a significant diagnostic challenge, as they may not be detected by conventional genetic studies and require interpretation supported by bioinformatic tools. We present the case of a pediatric patient with postnatal short stature and progressive genu varum. Biochemical studies revealed hypophosphatemia with reduced tubular reabsorption of phosphate, while calcium, parathyroid hormone (PTH), and vitamin D levels were within normal ranges. Radiological findings were consistent with rickets. Initial clinical exome sequencing was negative. Subsequently, a targeted gene panel identified a previously unreported intronic variant in the PHEX gene (c.1768+4dup; chrX:22,219,105 T>TA). In silico analysis using SpliceAI demonstrated a high probability of donor splice site loss (DS_DL = 0.80), while Pangolin predicted a splice-disrupting effect (score = 0.72); collectively, these findings support a deleterious effect on mRNA splicing. This case highlights the importance of integrating clinical, biochemical, genetic, and computational data for the interpretation of noncanonical intronic variants, expanding the mutational spectrum described for PHEX in XLH.
PMID:
42763725
Bibliographic data and abstract were imported from PubMed on 20 Sep 2026.
Read full publication at:
Please sign in
to see all details.
Advertisement
Stats
- Recommendations n/a n/a positive of 0 vote(s)
- Views 8
- Comments 0