A Mild Presentation of X-Linked Hypophosphatemia Caused by a Non-Canonical Splice Site Variant in the PHEX Gene.
Genes (Basel)
; 15(6)2024 May 24.
Article
in En
| MEDLINE
| ID: mdl-38927615
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pedigree
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RNA Splice Sites
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Familial Hypophosphatemic Rickets
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PHEX Phosphate Regulating Neutral Endopeptidase
Limits:
Adult
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Female
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Humans
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Male
Language:
En
Journal:
Genes (Basel)
Year:
2024
Document type:
Article
Affiliation country:
España