Whole-genome sequencing (WGS) for rare disease offers three key advantages over other genetic testing methods:
Especially important for rare disease cases, whole-genome sequencing is the most comprehensive test for detecting multiple variant types in a single assay.1–8 In a large, randomized controlled trial, the median time to diagnosis in neonatal intensive and pediatric intensive care patients was 13 days with WGS, compared to 107 days with standard testing.9
WGS testing performed in the Illumina Clinical Services Laboratory represents individuals enrolled in disease-specific clinical trials or as part of philanthropic efforts. As such, the percentage represented here may not be typical of that seen in a standard laboratory. This data is based on 669 total cases.
Whole-genome sequencing for rare disease has the power to help doctors diagnose genetic diseases quickly, helping families avoid long diagnostic odysseys. Of all genomic testing methods, WGS offers the highest likelihood of finding a diagnosis.10 It provides the highest coverage of the human genome, not only in regions not covered by other methods, but even within regions targeted by other methods.11,12 This increased coverage at first-line usage has been shown to reduce the need for unnecessary iterative tests and reduce the length of stay in the NICU.13,14
WGS can also impact patient care. A change in management has been reported in 49–75% of pediatric outpatients who received a diagnosis by WGS.15,16
Sawyer was admitted to the NICU at birth, but he and his family left the hospital without a diagnosis. The next 8 years involved failed targeted sequencing, chromosomal microarray analysis (CMA), and whole-exome sequencing tests. Finally, whole-genome sequencing identified a TRIP12 variant causing Sawyer’s condition.Watch Video
After seven years and dozens of specialists, genetic tests, and MRIs, Sophia and her family were exhausted and left without an answer. Two years later, WGS enabled Sophia’s medical team to identify a WDR45 mutation and diagnose her with Beta-propeller protein-associated neurodegeneration (BPAN).Watch Video
This course offers an overview of pediatric rare disease, available testing options, and clinical implementation of genomic sequencing. It may be relevant to laboratory providers, healthcare providers, healthcare organizations, and others interested in a review of genomics in the rare disease population. This course was made possible through an educational grant from Illumina.View Course Details
Dr. Christian Marshall of The Hospital for Sick Children explains how laboratory and clinical best practices can enable whole-genome sequencing for genetic disease diagnosis.
Dr. Vandana Shashi of Duke University and Kimberly LeBlanc of the Undiagnosed Diseases Network discuss how WGS can short-circuit the diagnostic odyssey for patients with rare disease.
Dr. Shimul Chowdhury of Rady Pediatric Genomic and Systems Medicine Institute explains how rapid WGS can help pinpoint the causes of rare disease in children.
NICUSeq is a multi-center research study evaluating whether the clinical management of acutely ill newborns is altered with WGS.Read Article
Project Baby Bear is a pilot program studying the use of WGS for rapid diagnosis and early treatment of infants at neonatal intensive care sites.Read Article
LeukoSEQ is a clinical trial designed to evaluate whole-genome sequencing as a first-line diagnostic tool for leukodystrophies.Read Article
WGS offers clear diagnostic benefits for patients with rare disease, but there are barriers to widespread adoption. The Medical Genome Initiative supports standards development for clinical WGS.
Different types of genetic variants underlie intellectual disability. This study evaluates WGS versus chromosomal microarray analysis (CMA) as a first-line diagnostic test.
The diagnostic odyssey is often amplified for patients in resource-limited areas. In this paper, the authors report on the impact of making WGS available to these patients.