Case Report: Deep intronic PHEX variant causing aberrant splicing identified by whole genome and targeted RNA sequencing in X-linked hypophosphatemia

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X-linked hypophosphatemia (XLH) is primarily caused by mutations in the PHEX gene, leading to renal phosphate wasting and impaired bone mineralization.
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A novel deep intronic variant in the PHEX gene was identified in a patient with XLH, causing aberrant splicing and premature stop codons.
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The patient had previously undergone extensive genetic testing without identifying a causative mutation over several years.
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Following the molecular diagnosis, the patient was treated with Burosumab, resulting in clinical improvement.
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This case emphasizes the importance of comprehensive genomic analysis and RNA sequencing in identifying undetected genetic causes of XLH.

Frontiers In Endocrinology

by Susanne Spranger, Helene Faust, Patricia Duffek, Susanna Schubert, Heyko Skladny, Peter Kovacs, Anke Tönjes, Denny Popp
July 9, 2026

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