Droplet digital PCR as a first-line detection tool in the genetic diagnosis of vascular anomalies.
14 affiliations
- 1Epilepsy Research Centre, Department of Medicine (Austin Hospital), University of Melbourne, 245 Burgundy Street, Heidelberg, VIC 3084, Australia.
- 2Victorian Clinical Genetics Services, 50 Flemington Rd, Parkville, VIC 3052, Australia.
- 3Murdoch Children's Research Institute, 50 Flemington Rd, Parkville, VIC 3052, Australia.
- 4Royal Children's Hospital Department of Paediatrics, University of Melbourne, 50 Flemington Rd, Parkville, VIC 3052, Australia.
- 5Tasmanian Clinical Genetics Service, 48 Liverpool St, Hobart, TAS 7000, Australia.
- 6The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3050, Australia.
- 7Department of Medical Biology, University of Melbourne, Grattan Street, Parkville, VIC 3010, AustraliaGrattan Street, Parkville, VIC 3010, Australia.
- 8Department of Plastic and Maxillofacial Surgery, Royal Children's Hospital, 50 Flemington Rd, Parkville, VIC 3052, Australia.
- 9Department of General Medicine, Royal Children's Hospital, 50 Flemington Rd, Parkville, VIC 3052, Australia.
- 10Department of Paediatrics, Monash University, Wellington Rd, Clayton, VIC 3800, Australia.
- 11Anatomical Pathology, St Vincent's Hospital, 41 Victoria Parade, Fitzroy, VIC 3065, Australia.
- 12Anatomical Pathology, Royal Children's Hospital, 50 Flemington Rd, Parkville, VIC 3052, Australia.
- 13Department of Dermatology, Royal Children's Hospital, 50 Flemington Rd, Parkville VIC 3052, Australia.
- 14Facial Sciences Research Group, Murdoch Children's Research Institute, 50 Flemington Rd, Parkville, VIC 3052, Australia.
Abstract
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.
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BibTeX
@article{lane2026droplet,
title = {{Droplet digital PCR as a first-line detection tool in the genetic diagnosis of vascular anomalies.}},
author = {Tara K Lane and Natasha J Brown and Timothy E Green and Denisse Garza and Michelle G de Silva and Mark F Bennett and Caitlin Tubb and Sian M W Macdonald and Adam Gascoigne and Roderic J Phillips and John Slavin and Colleen D'Arcy and Duncan MacGregor and Amelia Clifford and Lydia Pathmanathan and Susan J Robertson and Phillip Bekhor and Jodie Simpson and Samuel Gooley and Ingrid E Scheffer and Samuel F Berkovic and Anthony J Penington and Michael S Hildebrand},
journal = {Human molecular genetics},
year = {2026},
month = oct,
doi = {10.1093/hmg/ddag109},
url = {https://europepmc.org/article/MED/42900767},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Droplet digital PCR as a first-line detection tool in the genetic diagnosis of vascular anomalies.
AU - Tara K Lane
AU - Natasha J Brown
AU - Timothy E Green
AU - Denisse Garza
AU - Michelle G de Silva
AU - Mark F Bennett
AU - Caitlin Tubb
AU - Sian M W Macdonald
AU - Adam Gascoigne
AU - Roderic J Phillips
AU - John Slavin
AU - Colleen D'Arcy
AU - Duncan MacGregor
AU - Amelia Clifford
AU - Lydia Pathmanathan
AU - Susan J Robertson
AU - Phillip Bekhor
AU - Jodie Simpson
AU - Samuel Gooley
AU - Ingrid E Scheffer
AU - Samuel F Berkovic
AU - Anthony J Penington
AU - Michael S Hildebrand
PY - 2026
DA - 2026/10/01
JO - Human molecular genetics
DO - 10.1093/hmg/ddag109
UR - https://europepmc.org/article/MED/42900767
AB - 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.
SN - 0964-6906
SN - 1460-2083
ER -