Diagnostic Yield of Targeted Hearing Loss Gene Panel Sequencing in a Large German Cohort With a Balanced Age Distribution from a Single Diagnostic Center: An Eight-year Study.
Anke Tropitzsch, Thore Schade-Mann, Philipp Gamerdinger and 11 others
PMID 34753855WHAT IT FOUND
Targeted gene panel sequencing diagnosed 25% of a large, age-balanced German hearing loss cohort.
Diagnostic yield rose to 42% in early-onset cases but fell to 12% in late-onset cases. Adding more genes to the panel did not significantly increase the diagnosis rate.
Key findings
01The overall diagnostic yield for targeted genetic testing was 25% across the entire cohort of 305 unrelated patients.
02Diagnostic rates varied significantly by age of onset, with 42% of early-onset cases receiving a genetic diagnosis compared to only 12% of late-onset cases.
03Expanding the gene panel from 95 to 164 genes resulted in a negligible increase in diagnostic yield, from 20.0% to 20.5%.
STILL TO COME
How it was doneWhat they foundWhat it means for SLPs
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What it does not show
The study is retrospective and single-center, limiting generalizability. The high proportion of late-onset cases in this age-balanced cohort differs from many other studies that focus on pediatric populations, affecting the overall yield compared to other literature. The diagnostic bottleneck remains variant classification, with 69% of variants being of uncertain significance. The study did not assess the clinical utility or cost-effectiveness of the testing, only the diagnostic yield.
Declared interests
The authors declared no external funding. The sequencing was performed in collaboration with CeGaT GmbH, a commercial laboratory, but the study states that this research received no external funding.
The easy way to misread this
Do not assume that larger gene panels automatically lead to better patient outcomes. This study showed that expanding the panel from 95 to 164 genes yielded almost no additional diagnoses, suggesting that the current bottleneck is interpreting variants rather than finding them.