'Missing' disease-causing variants in Alport syndrome - PubMed
7 hours ago
- #kidney disease
- #genetic testing
- #Alport syndrome
- Up to 20% of clinically suspected Alport syndrome cases lack identified disease-causing variants.
- Reasons for missing variants include variants of uncertain significance, phenocopies, technical sequencing issues, and challenges in detecting non-canonical splicing variants.
- Methods to resolve uncertain variants include clinician-laboratory consultations, family studies, functional assays, and bioinformatics prioritization followed by RNA sequencing or splicing assays.
- Patients without confirmed variants should be managed as Alport syndrome cases until diagnosis is confirmed.
- The inability to detect all disease-causing variants leads to underestimation of genetic contributions to kidney diseases.