A Mild Presentation of X-Linked Hypophosphatemia Caused by a Non-Canonical Splice Site Variant in the PHEX Gene
Por:
Fraga, G, Herreros, MA, Pybus, M, Aza-Carmona, M, Pilco-Teran, M, Furlano, M, García-Borau, MJ, Torra, R, Ars, E
Publicada:
1 jun 2024
Resumen:
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.
Filiaciones:
Fraga, G:
Univ Autonoma Barcelona, Hosp Santa Creu i St Pau, Inst Recerca St Pau IR St Pau, Pediat Nephrol Dept,RICORS SAMID, Barcelona 08193, Catalonia, Spain
Herreros, MA:
Univ Autonoma Barcelona, Inst Recerca St Pau IR St Pau, Nephrol Dept,Fundacio Puigvert, RICORS2040 Kidney Dis,Dept Med, Barcelona 08193, Catalonia, Spain
Pybus, M:
Inst Recerca St Pau IR St Pau, Mol Biol Lab, Fundacio Puigvert, RICORS2040 Kidney Dis, Barcelona 08193, Catalonia, Spain
Aza-Carmona, M:
Inst Recerca St Pau IR St Pau, Mol Biol Lab, Fundacio Puigvert, RICORS2040 Kidney Dis, Barcelona 08193, Catalonia, Spain
Pilco-Teran, M:
Univ Autonoma Barcelona, Inst Recerca St Pau IR St Pau, Nephrol Dept,Fundacio Puigvert, RICORS2040 Kidney Dis,Dept Med, Barcelona 08193, Catalonia, Spain
Furlano, M:
Univ Autonoma Barcelona, Inst Recerca St Pau IR St Pau, Nephrol Dept,Fundacio Puigvert, RICORS2040 Kidney Dis,Dept Med, Barcelona 08193, Catalonia, Spain
García-Borau, MJ:
Univ Autonoma Barcelona, Hosp Santa Creu i St Pau, Pediat Dept, Neonatol Unit, Barcelona 08193, Catalonia, Spain
Torra, R:
Univ Autonoma Barcelona, Inst Recerca St Pau IR St Pau, Nephrol Dept,Fundacio Puigvert, RICORS2040 Kidney Dis,Dept Med, Barcelona 08193, Catalonia, Spain
Ars, E:
Inst Recerca St Pau IR St Pau, Mol Biol Lab, Fundacio Puigvert, RICORS2040 Kidney Dis, Barcelona 08193, Catalonia, Spain
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