Osteogenesis Imperfecta — 'brittle bone disease' spanning a severity spectrum from occasional fractures to perinatal lethality, where the specific type I collagen variant determines prognosis, treatment approach, and recurrence risk for future pregnancies.
Whole genome sequencing evaluates COL1A1, COL1A2, and all 20+ additional OI-related genes — providing the molecular diagnosis that determines OI type classification, severity prognosis, and inheritance pattern for genetic counseling.
Osteogenesis Imperfecta
Osteogenesis imperfecta (OI) is a group of heritable connective tissue disorders primarily caused by pathogenic variants in COL1A1 (chromosome 17q21.33) or COL1A2 (chromosome 7q21.3), encoding the α1 and α2 chains of type I collagen respectively. Type I collagen is the most abundant structural protein in bone, skin, tendons, and sclerae. OI is classified into types I-V (Sillence classification) based on clinical severity, with additional molecular subtypes (types VI-XX) defined by variants in non-collagenous genes involved in collagen processing, bone mineralization, and osteoblast function. Overall prevalence is approximately 1 in 10,000-20,000.
OI type I (mild, quantitative collagen deficiency from null COL1A1 alleles) causes bone fragility with blue sclerae, near-normal stature, and fractures that decrease after puberty. Type II (perinatal lethal) causes multiple in utero fractures, severe skeletal deformity, and death in the perinatal period. Type III (progressive deforming) causes severe bone fragility, progressive skeletal deformity, very short stature, and wheelchair dependence. Type IV (moderate) falls between types I and III. The specific COL1A1/COL1A2 variant — particularly whether it causes a quantitative deficiency (haploinsufficiency, typically milder) vs. a structural defect (glycine substitution in the collagen triple helix, typically more severe) — is the primary determinant of disease severity.
Treatment includes cyclic intravenous bisphosphonates (pamidronate, zoledronate − standard of care for moderate-severe OI, increasing bone density and reducing fracture rate), orthopedic management including intramedullary rodding of long bones, physical therapy, and hearing assessment (progressive hearing loss occurs in ~50% of adults with OI). Newer therapies in development include anti-sclerostin antibodies (romosozumab), anti-RANKL therapy (denosumab, showing benefit in pediatric OI studies), and gene therapy approaches targeting dominant-negative COL1A1/COL1A2 alleles.
Recessive OI (types VI-XX) is caused by variants in non-collagenous genes including SERPINF1, CRTAP, P3H1, PPIB, BMP1, IFITM5, and others — these are missed by COL1A1/COL1A2-only testing.
COL1A1 and COL1A2 account for ~85-90% of OI, but 20+ additional genes cause recessive and atypical forms. Single-gene testing misses recessive OI. Whole genome sequencing evaluates the complete molecular landscape.
The specific collagen variant type — haploinsufficiency vs. glycine substitution — determines severity prognosis
COL1A1 null alleles (frameshift, nonsense, splice site variants that produce premature stop codons) cause quantitative collagen deficiency — typically mild OI type I with blue sclerae and reduced fracture risk after puberty. In contrast, glycine substitutions in the Gly-X-Y repeat of the collagen triple helix (particularly in the α1 chain C-terminal region) cause structural collagen defects that produce moderate to severe OI (types II-IV). This genotype-severity correlation enables prognostic counseling at the time of molecular diagnosis — information that is not available from clinical assessment alone in a newborn or fetus with a prenatal fracture.
Prenatal fractures on ultrasound can be OI type II (lethal) or type III (survivable) — molecular diagnosis distinguishes them
Prenatal ultrasound may detect multiple fractures, shortened limbs, or thoracic hypoplasia in the second trimester. The critical clinical question is whether this represents OI type II (perinatal lethal, typically caused by de novo dominant COL1A1/COL1A2 glycine substitutions) or OI type III (severe but survivable, also caused by collagen structural defects). The distinction has profound implications for management counseling. Molecular diagnosis from amniocentesis or CVS can identify the specific variant and — based on published genotype-phenotype data — provide evidence-based severity prediction that ultrasound alone cannot supply.
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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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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.
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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.
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Ships within 48 hours · Results in 6–8 weeks
