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| Home > Articles > Published articles > A Mild Presentation of X-Linked Hypophosphatemia Caused by a Non-Canonical Splice Site Variant in the PHEX Gene |
(Institut de Recerca Sant Pau) (Institut de Recerca Sant Pau) (Institut de Recerca Sant Pau) (Institut de Recerca Sant Pau) (Institut de Recerca Sant Pau) (Institut de Recerca Sant Pau) (Institut de Recerca Sant Pau)| Date: | 2024 |
| Abstract: | X-linked hypophosphatemia (XLH) is a rare inherited disorder of renal phosphate wasting with a highly variable phenotype caused by loss-of-function variants in the PHEX gene. The diagnosis of individuals with mild phenotypes can be challenging and often delayed. Here, we describe a three-generation family with a very mild clinical presentation of XLH. The diagnosis was unexpectedly found in a 39-year-old woman who was referred for genetic testing due to an unclear childhood diagnosis of a tubulopathy. Genetic testing performed by next-generation sequencing using a kidney disease gene panel identified a novel non-canonical splice site variant in the PHEX gene. Segregation analysis detected that the consultand's father, who presented with hypophosphatemia and decreased tubular phosphate reabsorption, and the consultand's son also carried this variant. RNA studies demonstrated that the non-canonical splice site variant partially altered the splicing of the PHEX gene, as both wild-type and aberrant splicing transcripts were detected in the two male members with only one copy of the PHEX gene. In conclusion, this case contributes to the understanding of the relationship between splicing variants and the variable expressivity of XLH disease. The mild phenotype of this family can be explained by the coexistence of PHEX transcripts with aberrant and wild-type splicing. |
| Grants: | Instituto de Salud Carlos III PI19/01633 Instituto de Salud Carlos III PI22/00361 Instituto de Salud Carlos III PI23/00426 Instituto de Salud Carlos III PT20/00196 Instituto de Salud Carlos III PMP21/00109 |
| Note: | Altres ajuts: Fundació La Marató de TV3 (202036-30); European Union-Next GenerationEU (RD21/0005/0001) |
| Rights: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.  |
| Language: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Subject: | X-linked hypophosphatemia ; PHEX gene ; Non-canonical splice site variant |
| Published in: | Genes, Vol. 15, Núm. 6 (May 2024) , ISSN 2073-4425 |
