Hereditary Angioedema — unpredictable, sometimes fatal swelling attacks that once carried 30% lifetime laryngeal mortality, now entirely preventable with molecular diagnosis and mechanism-targeted therapy.
Whole genome sequencing identifies all hereditary angioedema molecular subtypes — SERPING1 variants (types 1 and 2), F12 variants (type 3), and ANGPT1/PLG variants — enabling selection among three distinct approved treatment mechanisms.
Hereditary Angioedema
Hereditary angioedema (HAE) is a potentially life-threatening genetic condition characterized by recurrent episodes of subcutaneous and submucosal edema, most commonly affecting the extremities, face, gastrointestinal tract, and larynx. HAE affects approximately 1 in 50,000 individuals worldwide, with autosomal dominant inheritance and uniform penetrance but highly variable expressivity. Laryngeal attacks are the most feared complication — untreated, HAE carries a historical mortality rate of approximately 30% from upper airway obstruction. With modern on-demand and prophylactic therapies, mortality can be effectively eliminated when the diagnosis is established.
HAE is genetically heterogeneous. The most common forms — HAE types 1 and 2 — are caused by SERPING1 pathogenic variants encoding C1 inhibitor. Type 1 (~85%) involves reduced C1-INH quantity; type 2 (~15%) involves normal or elevated quantity but dysfunctional protein. Both types are diagnosed by measuring C1-INH level and functional activity, together with reduced C4 complement levels. HAE type 3 (HAE with normal C1-INH), primarily affecting women and often triggered or worsened by estrogen, is caused by pathogenic variants in F12 (factor XII) in approximately 25% of cases; other cases have variants in ANGPT1 (angiopoietin-1), PLG (plasminogen), KNG1, or MYOF, with the remainder genetically unresolved. HAE type 3 characteristically has normal complement studies, making its diagnosis entirely gene-dependent.
The treatment landscape for HAE has been transformed by multiple mechanism-specific approved therapies: C1 inhibitor concentrate replacement (HAEGARDA, Berinert, Ruconest), plasma kallikrein inhibitor (lanadelumab for prophylaxis, subcutaneous icatibant for on-demand), bradykinin receptor antagonist (icatibant), and most recently garadacumab and donidalorsen. Treatment selection and dosing may be influenced by molecular subtype — for example, HAE type 3 patients often have different trigger profiles and hormonal sensitivity that inform management. All approved therapies provide protection regardless of SERPING1 vs F12 genotype, but the emerging precision medicine landscape increasingly rewards precise molecular diagnosis.
HAE with normal C1-INH (type 3) has normal complement studies and is invisible to standard biochemical HAE testing. Only molecular genotyping can confirm the diagnosis in this subtype — and a confirmed F12, ANGPT1, or PLG variant guides management and enables family cascade testing.
HAE type 3 with normal C1-INH has normal complement studies and is undetectable by standard biochemical testing. Molecular diagnosis is the only path to confirmation — and whole genome sequencing evaluates all known HAE genes in one test.
HAE type 3 is completely missed by standard complement testing — only gene sequencing can confirm it
Standard HAE diagnosis relies on biochemical measurements: C1-INH antigenic level, C1-INH functional activity, and C4. These tests reliably identify HAE types 1 and 2, both caused by SERPING1 variants with C1-INH deficiency. However, HAE type 3 — which may affect as many as 1 in 100,000 women — has entirely normal C4, C1-INH level, and C1-INH function. Women with recurrent unexplained angioedema, normal complement studies, and symptoms that worsen with oral contraceptives, pregnancy, or HRT may have HAE type 3 and remain undiagnosed for years. Molecular testing of F12, ANGPT1, and PLG is the only path to confirming this diagnosis.
Knowing the precise SERPING1 variant enables family cascade testing and stratifies novel therapy eligibility
Emerging HAE therapies — including RNA interference approaches targeting plasma kallikrein — have been developed with mechanism specificity that may translate into differential response by HAE subtype. SERPING1 variant type (missense, null, splicing) is associated with HAE type 1 vs type 2 classification, which informs interpretation of C1-INH functional assays. Family cascade testing — identifying at-risk relatives before a first laryngeal attack — prevents deaths and requires knowing the precise familial variant. Whole genome sequencing provides the complete SERPING1 coding and intronic sequence, detecting all variant types including large deletions that account for approximately 10-20% of SERPING1 pathogenic variants.
Your full DNA (not just a part of it)
Traditional genetic testing looks at narrow sets of genes, missing most parts of your genome. We sequence your full genome — every gene and every region between genes.
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Easy to read and with answers you and your doctor can act on. Not a file to interpret — 200+ clinical reports, organized by category.
Your test becomes more valuable every year
Your DNA does not change, but genome science is accelerating. Every month, new variant-disease associations are discovered. We validate these findings and update your reports automatically. Your test becomes more valuable every year.
The results doctors bring to their hardest cases.
Forty years of uncertainty. One test.
A patient had spent decades in the UK healthcare system without a diagnosis. Dante data, accepted by NHS clinical teams at Queen Elizabeth University Hospital Glasgow, identified Noonan Syndrome and a RUNX1 leukemia-associated variant that had gone undetected. After 40 years, they finally had an answer.
A complete read delivers a complete picture.
A patient came to Dante to investigate periodic paralysis. Reading the complete genome identified a concurrent hereditary cardiac finding — Brugada syndrome — that their doctor confirmed with an ECG. The result also explained a family member's unresolved cardiac history. One test. Every answer in it.
Sequenced in 2019. The data worked in 2021.
Jennifer sequenced her genome with Dante two years before her breast cancer diagnosis. When treatment began, Dante's pharmacogenomics data showed her prescribed chemotherapy would cause serious adverse effects. Her doctor selected an alternative — and she started effective treatment from day one.
Every genetic question deserves a complete answer.
Whether you are searching for answers today or protecting your health for tomorrow, a complete read of your entire genome is the only place to start.
It runs in your family. Now you can know if it runs in your genes.
Your genome contains inherited variants associated with medical conditions like cardiac, cancer, and neurological. We read all of them — with the clinical depth to give the result meaning.
Learn more →When traditional lab tests say you're fine. And you know you're not.
Standard diagnostic tests check for a pre-selected set of answers. We sequence your full DNA — including parts that no test was designed to check. If the answer is in your genome, we will help you find it.
Learn more →Your diagnosis may be right. Your treatment plan may be incomplete.
Your genes determine which treatments are most likely to work — and which are not. We give your doctor the tools and insights to inform your treatment plan.
Learn more →You want to know before something forces the question.
Some people don't wait for a diagnosis or a family history to act. Whole genome sequencing gives you the complete genetic picture now — so you and your doctor can make informed decisions before anything becomes urgent.
Learn more →You already took a DNA test. Here's what it couldn't tell you.
Most consumer DNA tests read less than 0.1% of your genome. We read all of it.
Learn more →Clinical-grade results. Chosen by individuals, trusted by doctors for their most complex cases.
Dante Genome Test helped specialists at a UK national acute hospital in the identification of Noonan Syndrome and a rare leukemia-associated genetic variant that had gone undetected. That result changed the medical care of the patient.
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Common questions about whole genome sequencing.
What is the difference between whole genome sequencing and a targeted genetic test?
Targeted genetic tests — including standard hereditary cancer panels — read a pre-defined list of known variants in a specific set of genes. They are designed to find what they already know to look for. Whole genome sequencing reads your entire genome: all 6 billion base pairs, every gene, every region between genes. A Mayo Clinic study published in JAMA Oncology found that standard testing guidelines missed more than half of patients with inherited cancer mutations. Genome Test does not have a fixed list.
What will I receive when my results are ready?
Your Dante Genome delivers 200+ physician-ready reports organized by clinical category — hereditary cancer, cardiac conditions, rare diseases, pharmacogenomics, carrier status, and more. Reports are delivered to your secure Genome Manager and are formatted for direct clinical use. Your genome data is permanently retained and re-analyzed automatically as science advances.
What happens if a clinically significant variant is found?
If a pathogenic or likely-pathogenic variant is identified, it will be clearly flagged in your physician-ready report with clinical context, published evidence, and recommended next steps. We recommend sharing any clinically significant finding with your physician or a genetic counselor, who can guide decisions about surveillance, risk reduction, or cascade testing for family members.
How is this different from a consumer DNA test like 23andMe or AncestryDNA?
Consumer DNA tests use genotyping chips that read less than 0.1% of your genome — a tiny pre-selected set of common variants. They are optimized for ancestry and population-level traits, not clinical genetic findings. The Dante Genome Test sequences 100% of your genome at 30X coverage, the same standard used in clinical diagnostic settings. The two tests are not comparable in scope, methodology, or clinical utility.
How long does it take to get results, and how are they delivered?
Your collection kit ships within 48 hours of ordering. Once your sample arrives at our CLIA-certified laboratory, sequencing and analysis takes 6–8 weeks. Results are delivered securely to your Genome Manager, where you can access your reports, share them with your physician, and receive automatic updates as new findings are validated against your genome.
We work with patient advocacy groups worldwide.
Dante Labs works with patient advocacy groups of any size — for Hereditary Angioedema and other conditions, rare and common. We support groups in any country, including virtual patient advocacy groups.
We can provide customized reports, group discounts, and packages tailored for your members. Please reach out using the form and we'll be in touch within two business days.
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One test.
A lifetime of answers.
One kit, sent to your home. Your entire genome sequenced at the clinical standard used for diagnostic decisions. 200+ physician-ready reports delivered to your Genome Manager in 6–8 weeks — permanent and updated as science advances.
Ships within 48 hours · Results in 6–8 weeks
