One test. Big picture. Brighter futures.

Meet Noah and Olivia. They found a diagnosis thanks to GeneDx’s unmatched dataset and commitment to finding answers for pediatric patients.

Meet Noah*

6 months old:
First symptoms
12 months old:
First referral
15 months old:
First genetic test
16 months old:
Uncertain results
2 years old:
Exome testing ordered

The start of answers:
Noah and his parents’ DNA samples arrive at GeneDx

Accessioning

As soon as FedEx makes its daily delivery, our accessioning team opens Noah and his parents’ sample collection boxes. They then:

Assign a unique accession number
Barcode each sample for tracking through our lab
Scan all included paperwork

Extraction

Our team isolates the pure DNA by separating it from proteins and other cellular components in Noah and his parents’ DNA samples.

They then evaluate the DNA for quantity and quality to improve accuracy and reliability of analysis.

Plating

Next, our team adds the DNA to plates for next generation sequencing.

A single plate includes the DNA for Noah, his parents, and dozens of other patients and relatives—all carefully tracked with unique identifiers.

Next generation sequencing

Samples are loaded into flow cells for next-generation sequencing.

Sequencers like the one shown here determine the exact DNA make up, which is then sent to our team for analysis.

Interpretation

The raw data for Noah and his parents’ samples moves into interpretation, where GeneDx’s expertise and world-leading dataset shine.

The GeneDx team first looks through Noah’s medical records to find the key descriptions, prior results, and other relevant information that will drive the analysis.

We then find and confirm relevant variants, classifying them as pathogenic, benign, or uncertain.

Finally, a diagnosis.

GeneDx definitively classifies Noah’s two variants in the CRELD1 gene as pathogenic. Armed with his GeneDx report, Noah’s geneticist diagnosed him with a CRELD1-related neurodevelopmental disorder associated with:

Developmental delay
Epilepsy
Hypotonia

Patients with this disorder also often have heart arrhythmia (~50% of patients) and frequent infections.

With his genetic diagnosis, Noah and his family now have:

More informed healthcare, including evaluation for cardiac arrhythmias

Realistic expectations about how Noah’s disease will likely evolve as he grows

Insight into the likelihood of having another child with the same disorder (25% risk)

Connection with other families though the CRELD1 patient advocacy group

Connection with researchers looking into improved treatment approaches

How was GeneDx able to report Noah’s pathogenic variant?

Through years of investment, we’ve built an unparalleled dataset that associates the symptoms and genetic variants of more than 1.5 million people—and counting.

The rich diversity of this genetic data means we can give more patients answers, thanks to all the patients tested before them. In Noah’s case, that meant Olivia and others like her.

Meet Olivia*

Two years before Noah’s test arrived at the GeneDx lab, Olivia received exome testing for developmental delay, low muscle tone, and epilepsy.

At the time of her testing, Olivia’s two CRELD1 variants were classified as variants of uncertain significance. Both variants had been seen in healthy individuals, indicating each variant alone was insufficient to cause her symptoms.

Internal GeneDx data suggested that Olivia’s results could potentially be pathogenic

Variants on one copy of the gene had been published in patients with an increased risk for a specific type of congenital heart defect.
Internal GeneDx data suggested variants on both copies of the gene could cause a more severe neurodevelopmental disorder.
GeneDx scientists and the ordering provider suspected the CRELD1 variants explained the features based on internal data, but a research collaboration was needed to know for sure.

Disease-gene discovery at GeneDx: Ending the diagnostic odyssey

Discovery

Candidate gene finding identified during analysis and reported

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Data sharing

GeneDx submits candidate gene finding to GeneMatcher

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Collaboration

GeneDx collaborates with external clinicians and researchers with interest in same gene

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Diagnostics

GeneDx offers reanalysis and provides updated report with diagnostic results

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Publication

Publication of cohort of patients enables candidate gene to be upgraded to disease-associated gene

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Consent

Family consents to participate in research

Publication of a new clinical disorder

After GeneDx submitted CRELD1 as candidate gene to GeneMatcher, an international collaboration studied multiple unrelated patients included with overlapping clinical features.

Combined with functional studies, the collaboration confirmed an association between Olivia’s variants and a genetic disorder causing developmental delay, epilepsy, and hypotonia.

Real impact: More answers for more patients

Thanks to the study, Olivia (and dozens like her) received an updated GeneDx report with a definitive result, ending their diagnostic odyssey—and paving the way for Noah’s pathogenic result.

Pay-it-forward data strategy: Patients helping other patients

With every patient tested at GeneDx, our underlying interpretation platform gets smarter and we can offer more answers to more patients.

The impact increases every single day, with each patient helping future patients find answers.

Move forward with confidence. Move forward with GeneDx.

Ready to find answers—and pay it forward?

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* Fictionalized case study for illustrative purposes only