Alagille Syndrome — a multisystem disorder affecting bile ducts, heart, skeleton, and eyes, where the first targeted therapy (maralixibat) was approved in 2021 and molecular confirmation guides both treatment eligibility and prognosis.
Whole genome sequencing evaluates both JAG1 and NOTCH2 — including the large deletions that account for 7% of JAG1 cases — providing the molecular diagnosis that standard sequencing-only panels may miss.
Alagille Syndrome
Alagille syndrome (ALGS) is an autosomal dominant multisystem disorder caused by pathogenic variants in JAG1 (~97% of cases, chromosome 20p12.2) or NOTCH2 (~2-3%, chromosome 1p12). JAG1 encodes a ligand in the Notch signaling pathway, which is critical for cell fate determination during embryonic development of bile ducts, heart, vasculature, skeleton, and eyes. Over 600 different JAG1 pathogenic variants have been reported, including missense, nonsense, frameshift, splice site variants, and whole-gene or multi-exon deletions (~7% of cases). ALGS affects approximately 1 in 30,000-50,000 births.
The cardinal features are bile duct paucity (intrahepatic cholestasis with severe pruritus, jaundice, and xanthomas), congenital heart defects (peripheral pulmonic stenosis in ~90%, complex cardiac defects in ~15%), butterfly vertebrae on spine radiographs, posterior embryotoxon on ophthalmological exam, and a characteristic facial appearance (prominent forehead, pointed chin, deep-set eyes). Clinical severity is highly variable — even within the same family carrying the identical JAG1 variant — ranging from subclinical liver involvement to liver failure requiring transplantation in approximately 15-20% of patients.
Maralixibat (Livmarli), an ileal bile acid transporter (IBAT) inhibitor, was approved by the FDA in 2021 for the treatment of cholestatic pruritus in Alagille syndrome patients aged 1 year and older. It reduces serum bile acid levels and significantly improves the debilitating pruritus that impairs quality of life. Odevixibat (Bylvay) is approved for progressive familial intrahepatic cholestasis (PFIC) and is under investigation for ALGS. Liver transplantation remains necessary for patients with progressive liver failure or intractable pruritus despite medical therapy.
Approximately 50-70% of ALGS cases are de novo — parents are unaffected. However, because of variable expressivity, apparently unaffected parents should be evaluated for subtle features (posterior embryotoxon, butterfly vertebrae) before concluding de novo status.
JAG1 whole-gene deletions account for 7% of Alagille syndrome and are missed by exon-sequencing panels. Whole genome sequencing detects both sequence variants and structural rearrangements in a single test.
7% of JAG1 pathogenic alleles are whole-gene or multi-exon deletions invisible to standard sequencing
Approximately 7% of Alagille syndrome patients carry large JAG1 deletions — ranging from single-exon to whole-gene deletions and occasionally extending into flanking genes. Standard Sanger sequencing or exon-only NGS panels do not detect copy number changes, returning a false-negative result in these patients. When a patient meets clinical criteria for ALGS but sequencing of JAG1 is negative, MLPA or chromosomal microarray must be ordered separately. Whole genome sequencing detects both sequence variants and copy number variants from the same data, eliminating this diagnostic gap and the associated time delay.
Molecular diagnosis enables cardiac surveillance planning — 15% of ALGS patients have complex heart defects requiring intervention
While peripheral pulmonic stenosis (present in ~90% of ALGS patients) is generally benign and often resolves with growth, approximately 15% of ALGS patients have complex congenital heart defects — tetralogy of Fallot, pulmonary atresia, ventricular septal defects — requiring surgical intervention. Cardiac evaluation is standard of care for all newly diagnosed ALGS patients. Molecular confirmation in an infant presenting with neonatal cholestasis triggers complete cardiac workup before the heart defect presents clinically. Without molecular diagnosis, cholestatic infants may be evaluated solely for biliary disease, missing concurrent cardiac pathology.
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.
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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 Alagille Syndrome 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.
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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
