Case Report: Deep intronic PHEX variant causing aberrant splicing identified by whole genome and targeted RNA sequencing in X-linked hypophosphatemia - Report - MDSpire
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Case Report: Deep intronic PHEX variant causing aberrant splicing identified by whole genome and targeted RNA sequencing in X-linked hypophosphatemia
Clinical Report: Identification of a Deep Intronic PHEX Variant in XLH
Overview
This case study reports the identification of a novel deep intronic variant in the PHEX gene in a patient with X-linked hypophosphatemia (XLH) who had previously undetectable genetic causes. The variant was confirmed to cause abnormal splicing, leading to a loss-of-function mechanism.
Background
X-linked hypophosphatemia (XLH) is a rare genetic disorder caused primarily by mutations in the PHEX gene, leading to phosphate metabolism dysregulation. Despite extensive genetic testing, some patients remain without identified causative variants, highlighting the limitations of current genetic testing methods. Recent advancements in genomic sequencing technologies have facilitated the discovery of previously unidentified variants.
Data Highlights
No numerical data or trial data was provided in the source material.
Key Findings
A novel deep intronic variant in the PHEX gene (c.2070 + 601C>T) was identified in a patient with XLH.
This variant was confirmed as de novo and caused two aberrant transcripts with pseudoexon inclusions.
The aberrant splicing resulted in premature stop codons, supporting the pathogenicity of the variant.
This case emphasizes the importance of comprehensive genomic analysis in patients with unexplained XLH.
It highlights the potential for RNA sequencing to identify deep intronic variants that standard testing may miss.
Clinical Implications
The identification of deep intronic variants through advanced genomic and RNA sequencing methods can enhance the diagnostic process for patients with XLH.
Conclusion
This case highlights the value of comprehensive genomic analysis in diagnosing XLH and the role of RNA sequencing in identifying previously undetected genetic variants.
