Nephrology · 47 min ago
Commentary Supports Evaluating Exome Sequencing as a First-Tier Kidney Test
A commentary in CJASN questions whether exome sequencing after a nondiagnostic kidney gene panel was a separate test or reanalysis of existing exome data. It argues that available findings do not show a diagnostic-yield disadvantage for first-tier exome sequencing, while emphasizing that prospective comparisons of cost and time to diagnosis are needed.
- ES yielded 33% in a small first-tier subgroup.
- Only 54 of 307 nondiagnostic-panel patients received ES.
- Authors call for prospective comparison of yield, cost and timing.
The authors discuss a research letter reporting a 13% incremental diagnostic yield from exome sequencing (ES) after nondiagnostic kidney gene panel testing. They note that the report does not clarify whether ES involved a new assay or broader analysis of existing exome data; the distinction affects cost, diagnostic delay and the feasibility of reflex testing. Only 54 of 307 patients with nondiagnostic panels underwent ES, potentially limiting the diagnoses detected. In the small, clinician-selected first-tier groups, diagnostic yield was 33% with ES (6/19) and 33% with panel testing (150/457). The authors also cite prior studies reporting ES yields of 9% in unselected adults with CKD and about 25% in adults with nephropathy of indeterminate origin.
The commentary argues that these data do not indicate a diagnostic penalty from starting with ES, which can also detect variant types or regions not covered by some panels. However, the first-tier comparison is small and selected, and ES has limitations, including restricted coverage of exons and flanking intronic regions. The authors call for a prospective multicenter comparison of testing pathways that measures diagnostic yield, time to diagnosis and cost; the commentary does not establish that first-tier ES should replace panel testing.
In practice
For patients being evaluated for suspected genetic kidney disease, the commentary supports considering the breadth of exome sequencing when choosing a testing pathway, but it does not establish first-tier ES as superior to gene panels. The reported first-tier yields were equal at 33%, but the ES group was small and clinician-selected; testing methods and costs are also unclear. The authors call for prospective multicenter comparisons of diagnostic yield, time to diagnosis and cost, so these data alone do not justify a change in testing practice.
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Clinical Journal of the American Society of Nephrology: Exome Sequencing as the First-Tier Test in Genetic Kidney Disease ↗This is an automated AI-condensed summary that has not yet been reviewed by an editor. Always consult the full item at the original source.