Ending the Rare and Hereditary Disease Diagnostic Odyssey: How ACTInherit Whole Genome Sequencing (WGS) Helps Uncover Answers

Why do some patients go throughyears of testing and still have no clear diagnosis?

For many families affected byrare and hereditary diseases, the search for answers becomes a long andexhausting diagnostic odyssey. Patients may undergo routine bloodtests, imaging studies, karyotyping, chromosomal microarray analysis (CMA), ortargeted gene panels over several years, yet still be left without a definitiveexplanation for their condition. The result is often ongoing uncertainty,delayed care decisions, and significant emotional and financial burden for families.

In this setting, whole genomesequencing (WGS) is emerging as an important tool in thediagnostic workup of complex and unresolved cases. ACTInherit,developed by ACT Genomics, is designed to provide a more comprehensive genomicview and help clinicians and families identify findings that may not becaptured by conventional testing approaches.

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Why can conventional testing still miss the cause?

Every genetic testing method hasstrengths, but also limitations. Whole exome sequencing (WES), for example,focuses primarily on the protein-coding regions of the genome, which make uponly a small portion of total human DNA. However, disease-causing variants inrare and hereditary diseases may also be found in non-coding regions or appearas more complex structural changes. As a result, some clinically relevantfindings may remain undetected when testing is limited to selected regions orvariant types.

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What advantages does ACTInherit (WGS) offer?

1. Comprehensive genome-wide analysis
ACTInherit analyzes the full genome in a single test, covering approximately 3billion DNA base pairs. This broader scope helps reduce the blind spotsassociated with tests that focus only on selected genes or genomic regions.

2. Broader variant detection in one workflow
ACTInherit is designed to detect multiple variant types, including singlenucleotide variants (SNVs), insertions/deletions (Indels), copy numbervariations (CNVs), structural variations (SVs), and mitochondrial DNAabnormalities. This more integrated approach may simplify the testing pathwayin complex cases.

3. More insight for unresolved cases
For patients with neurodevelopmental delay, congenital anomalies, suspectedhereditary disorders, or family histories suggestive of genetic disease, WGSmay help identify deep intronic variants and chromosomal structuralabnormalities that other approaches could miss.

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Who may benefit from ACTInherit (WGS)?

ACTInherit may be worthdiscussing with a clinician or genetics professional in cases where:

• Symptoms remain unexplained after multiple tes
• Prior genetic testing has been inconclusive
• A hereditary condition is suspected
• Thereis a family history suggestive of genetic disease
• Thepatient presents with complex phenotypes such as congenital anomalies orneurodevelopmental concerns

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Why does a diagnosis matter?

For families facing rare andhereditary diseases, a diagnosis is not the end of the journey. It is often thebeginning of more informed care. A clearer molecular diagnosis can supportclinical management, prognosis evaluation, and genetic counseling, while alsohelping families make better-informed decisions about future care planning.

As genomic medicine advances,clinicians and families now have better tools to explore the full picture ofthe genome. ACTInherit (WGS) is more than an additional test option. It is a morecomprehensive diagnostic approach for complex and unresolved cases.For families still searching for answers, a broader genomic perspective may bethe step that brings greater clarity.

To learn more about ACTInherit Whole Genome Sequencing (WGS),please contact ACT Genomics’ genetic counseling team: mailto:service@actgenomics.com

Disclaimer

This content is provided for medical information purposes only and does notconstitute medical advice or treatment recommendations. Actual testing andtreatment decisions should be made by qualified healthcare professionals basedon each patient’s individual condition and the most current clinical evidence.

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