Rapid Targeted Sequencing Using Dried Blood Spot Samples for Patients With Suspected Actionable Genetic Diseases

Area of Science:

• Genomics
• Medical Diagnostics
• Rare Diseases

Background:

• Advanced genome sequencing technologies improve diagnostic efficiency for rare genetic diseases.
• Early diagnosis of treatable rare genetic diseases can significantly alter patient management and prognosis.
• Ethical considerations and turnaround time are critical factors in genetic diagnostics.

Purpose of the Study:

• To design and evaluate an automated targeted sequencing platform to expedite the diagnosis of treatable rare genetic diseases.
• To address ethical concerns and reduce diagnostic turnaround time using a novel sequencing approach.
• To identify medically actionable genetic conditions amenable to timely intervention.

Main Methods:

• Development of an automated sequencing platform utilizing dried blood spot samples.
• Design of the NEOseq_ACTION panel, encompassing 254 genes linked to treatable Mendelian diseases.
• Validation through retrospective analysis of 24 patients and prospective analysis of 111 patients with suspected actionable genetic diseases.

Main Results:

• Prospective validation identified medically actionable diseases in 13.5% of patients.
• Diagnosed conditions included various metabolic disorders (e.g., acyl-CoA dehydrogenase deficiencies, hyperphenylalaninemia) and other genetic syndromes.
• The automated pipeline achieved a turnaround time of less than 4 days from sample collection to result reporting.

Conclusions:

• This pilot study demonstrates the feasibility of rapid, timely diagnosis for treatable rare genetic diseases.
• The automated analytic pipeline enhances the clinical utility of targeted sequencing for actionable genes.
• The developed strategy facilitates appropriate and prompt treatment for patients with rare genetic diseases.