AI Insight
This study evaluated droplet digital PCR (ddPCR) as a first-line diagnostic tool for vascular anomalies by testing 138 individuals for 46 recurrent pathogenic variants across 16 genes. The ddPCR detected disease-causing variants in 51% of cases, with an overall diagnostic yield of 75% when combined with follow-up sequencing methods. The most commonly identified variants were in PIK3CA, TEK, GNAQ, and MAP2K1 genes.
Why it matters
This approach offers a faster and more cost-effective initial diagnostic method for vascular anomalies compared to traditional next-generation sequencing, which is particularly valuable as targeted precision therapies become more widely available for these conditions. The high detection rate of recurrent variants suggests ddPCR could streamline clinical diagnosis and enable earlier treatment decisions.
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⚠️ Preprint – Noch nicht peer-reviewed
Dieser Artikel wurde noch nicht von unabhängigen Experten begutachtet. Die Ergebnisse sind vorläufig und sollten mit Vorsicht interpretiert werden.
Targeted precision therapies are increasingly used in the treatment of individuals with vascular anomalies (VAs). This increases the need for rapid, accurate and inexpensive genetic diagnosis. Droplet digital polymerase chain reaction (ddPCR) is an alternative to next-generation sequencing (NGS), permitting rapid, highly sensitive interrogation of recurrent pathogenic mosaic variants. We examined the feasibility of ddPCR as a primary diagnostic tool in a large cohort of individuals with VAs. Lesional tissue was collected for ddPCR of up to 46 recurrent pathogenic variants across 16 genes associated with VAs. Specimens were assessed on a subset of assays for each individual based on clinical phenotype. Most individuals who had negative ddPCR results went on to high-depth gene panel or deep exome NGS, or Sanger sequencing. Here we report the phenotypic and molecular findings for 78 newly recruited and tested individuals in addition to the 60 individuals already reported from our cohort. The overall diagnostic yield for our cohort when combined with individuals previously reported was 104/138 (75%). Of 138 individuals tested, recurrent pathogenic variants were detected in 71 (51%) on ddPCR. Variants were most frequently identified in PIK3CA (n=28), TEK (n=18), GNAQ (n=12), or MAP2K1 (n=7). In a further 33 individuals, pathogenic variants were identified on NGS or Sanger sequencing. Our findings indicate that ddPCR is an efficient method achieving a high diagnostic yield in our cohort when used prior to sequencing.
Source: Droplet Digital PCR as a First-Line Detection Tool in the Genetic Diagnosis of Vascular Anomalies