Increasing the accuracy and decreasing the time required for clinical genetic analysis

Bambino Gesù Children's Hospital

Increasing the accuracy and decreasing the time required for clinical genetic analysis

April 11, 2019

The Case:

In 2017, The genetic team at the largest pediatric hospital in Europe, Prof Antonio Novelli and his team of geneticists used to analyze dozens of rare genetic disorder cases per month.

Geneyx Solution:

Since the hospital adopted the Geneyx Analysis platform they are analyzing hundreds of cases each month, with the same team. Last month Dr. Novelli reported turn-around-time of 1-10 min (!) and diagnostic yields of over 65%, (!) doubling the global standard.

Prospective scalability:

Identifying the causal genetic mutation in such cases, presented in neonatal and pediatric intensive care units (NICU and PICU), is crucial for applying the right treatment which can be lifesaving. Increasing the accuracy (diagnostic yield) and decreasing the time required for the genetic analysis (turn-around-time) are key to the work of the geneticists in these cases. Today we are working with more than 20 children hospitals, in Italy, China, Hong Kong, Israel, and others.

See Geneyx In Action

Detecting Uniparental disomy (UPD) with Geneyx Analysis

UPD occurs at a frequency of 1 in 2000 individuals worldwide (1). The most well-known conditions of UPD include Prader-Willi syndrome, characterized by binge-eating and obesity, and Angelman syndrome, which causes intellectual disability and impaired speech

Confirming Achromatopsia Diagnosis with Geneyx Analysis

One complex case they encountered was a female of Ethiopian descent that was diagnosed with achromatopsia. To confirm the clinical diagnosis, next-generation sequencing was performed. The fastq files were processed using the secondary pipeline integrated with Geneyx, and the VCF files were then annotated and analyzed using Geneyx Analysis.

Applying Geneyx for high-throughput diagnostic settings

Implementation of Geneyx Analysis allowed customized gene panels with automatic reporting capabilities to easily accommodate for their large sample workflows. Coupled with this workflow automation, was the requirement to have customized reports. The Geneyx team was able to provide their customization requests to render reports using dynamic and static information

Identifying multi-nucleotide variants associated with congenital hypotonia and global developmental delay

WGS identified a likely pathogenic, de novo variant in POLR2A, which has a strong association with the phenotype displayed by the individual. The variant was adjacent to a polymorphism variant that was inherited from one of the parents, and this caused their in-house pipeline to mis-identify it as an inherited MNV in the exome sequencing analysis. The WGS findings led to a positive finding that could be presented to the patient.

Identifying a unique novel genetic event for juvenile Parkinson

With their current platform, they achieve a diagnostic yield of approximately 50%, and for the remaining undiagnosed cases, they choose to implement Geneyx Analysis. One complex case they encountered was a large family presenting with early onset Parkinson’s disease (Juvenile Parkinson), which affected several siblings born to closely related parents. The team had sent 10 samples for exome sequencing, which was the standard and most comprehensive genetic test available for clinical diagnostics. However, the results from exome sequencing were inconclusive, so they implemented whole genome sequencing on a subset of the family and analyzed the data with Geneyx.

Identifying novel mutations responsible for colon cancer predisposition

Prof Revital Kariv, M.D., and her team diagnose and treat patients with colon cancer. In many cases, they identify families with a clear predisposition to develop polyposis and thereafter colon cancer quite early in their lives, implying a strong inherited genetic background for the trait.

Better Data for Better Health

Bambino Gesù Children's Hospital