Whole genome sequencing (WGS) identifies almost all changes in a patient’s DNA by sequencing both the entire protein coding and the non-coding regions of the genome.
Today there are millions of patients suffering from misdiagnosed or undiagnosed genetic diseases as a result of insufficient genetic testing. Although in certain cases approaches like single gene testing, panel testing, or microarrays can identify the cause of a disease, these analyses are ultimately limited and can fail to reveal the full genetic cause. WGS, in contrast, overcomes such limitations and is the only test that can detect nearly all types of disease-causing genetic variants in one single test.

WGS is recommended for patients when:

1. 1. The symptoms are very broad, complex, or unspecific, not pointing towards specific disease or typical phenotype

Examples:

1. 1. • Clinical or genetic heterogeneity (e.g., intellectual disability/developmental delay, epilepsy, muscular dystrophies/muscular disorders, ataxia, neuropathies, cardiomyopathies, skeletal dysplasias, immunodeficiency, deafness, blindness).
      • Diseases or patients with atypical clinical presentations or phenotypes (e.g., patient with intracranial aneurysm due to PKD1 gene – polycystic kidney disease).
      • Patients with `blended’ clinical presentations and clinical suspicion of dual diagnosis ( e.g., patient with deafness and ichthyosis, intellectual disability and severe immunodeficiency).
      • Suspected of a microdeletion or microduplication syndrome (e.g., patients with neurodevelopmental delay, multiple dysmorphisms and/or malformations, growth delay).
      • Suspected mitochondrial disease (e.g., patient with muscular weakness, cardiomyopathy, visual problems).
   2. Suspected mitochondrial disease (e.g., patient with muscular weakness, cardiomyopathy, visual problems)

Examples:

1. 1. • Patient with autosomal dominant spastic paraplegia and with a negative result for the gene panel.
      • Patient with neurodevelopmental delay, with similarly affected siblings, and a negative testing with microarrays and WES.
      • Any case with suspected genetic disease and negative WES.
   2. A fast diagnosis is a medical necessity and there is not always the time for serial testing strategies

Examples:

1. • Patients severely ill for whom a diagnosis may direct or alter medical management (e.g., children with seizures, hypotonia, neurological abnormalities, and a rapidly deteriorating clinical status).
   • Newborns, babies and children where a rapid diagnosis is crucial for prognosis and treatments decisions (e.g., critically ill newborns and children in the neonatal and pediatric intensive care NICU and PICU).