TBX5 Full Length Gene Sequence Analysis (Holt-Oram Syndrome) Test
About TBX5 Full Length Gene Sequence Analysis (Holt-Oram Syndrome) Test
| Field | Value |
|---|---|
| Also Known As | TBX5 Gene Sequencing Test, TBX5 Mutation Analysis, Holt-Oram Syndrome Genetic Test, HOS Gene Test, Heart-Hand Syndrome Genetic Test |
| Sample Type | Chorionic villus (CVS), amniotic fluid, peripheral blood, or cord blood |
| Fasting Required | No fasting required |
| Report Time | 20 days |
| Recommended For | All ages; individuals with suspected Holt-Oram syndrome, family members of affected individuals, and at-risk pregnancies |
| Price | Starting at ₹24,000 |
What Is a TBX5 Full Length Gene Sequence Analysis (Holt-Oram Syndrome) Test?
The TBX5 full length gene sequence analysis (Holt-Oram syndrome) test examines the entire TBX5 gene to identify mutations that cause Holt-Oram syndrome (HOS), a rare inherited condition affecting the heart and upper limbs. The TBX5 gene, located on chromosome 12, plays a key role in the development of the heart and arms during early growth in the womb. This test is prescribed for individuals with suspected HOS, their family members, and for prenatal diagnosis in families with a known TBX5 mutation. This test is performed on a blood sample or, in prenatal cases, on chorionic villus, amniotic fluid, or cord blood. It is also called the TBX5 gene sequencing test, TBX5 mutation analysis, Holt-Oram syndrome genetic test, HOS gene test, or heart-hand syndrome genetic test.
What Does a TBX5 Full Length Gene Sequence Analysis (Holt-Oram Syndrome) Test Measure?
The TBX5 full length gene sequence analysis (Holt-Oram syndrome) test procedure involves analysing the TBX5 gene for changes that disrupt its normal function. The test looks for the following:
| What Is Analysed | What It Tells Us |
|---|---|
| TBX5 gene sequence (full length) | Detects single nucleotide changes, small insertions, and deletions across the entire gene |
| Copy number variants | Identifies larger deletions or duplications within the gene |
| Variant classification | Reports variants as pathogenic, likely pathogenic, or of uncertain significance (VUS) |
| Mutation type | Identifies missense, frameshift, nonsense, and splice-site mutations, particularly in the T-box domain (the region of the gene responsible for binding DNA) |
The test uses Sanger sequencing methodology and achieves greater than 99% sensitivity for detected variants.
Why Is a TBX5 Full Length Gene Sequence Analysis (Holt-Oram Syndrome) Test Done?
A doctor may request this test when a patient or their family member shows signs associated with Holt-Oram syndrome. It can also be used to clarify a diagnosis or guide family planning decisions.
Common Symptoms That May Require This Test
The following signs and symptoms may lead a doctor to recommend the Holt-Oram syndrome genetic test:
- Abnormally shaped or underdeveloped bones in the upper limbs (arms or forearms)
- Wrist (carpal) bone abnormalities visible on X-ray
- Missing, fused, or abnormally formed thumb
- Partial or complete absence of forearm bones
- Underdeveloped upper arm bone, collar bone, or shoulder blades
- Congenital heart defects such as atrial septal defect (ASD, a hole between the heart's upper chambers) or ventricular septal defect (VSD, a hole between the lower chambers)
- Abnormal heart rhythm, unusually slow heart rate (bradycardia), or irregular contractions (fibrillation)
Conditions This Test Can Help Detect
This test can help identify or confirm the following conditions:
- Holt-Oram syndrome, an autosomal dominant condition (meaning one copy of the altered gene is enough to cause the condition) affecting the heart and upper limbs
- Congenital heart defects, particularly atrial septal defects, which occur in patients with TBX5 variants
- Cardiac conduction abnormalities, including atrioventricular block and atrial fibrillation, which affect the electrical signals coordinating heartbeats
How to Prepare and What to Expect
The TBX5 full length gene sequence analysis (Holt-Oram syndrome) test procedure is straightforward. The steps below explain what to do before and during sample collection.
Do You Need to Fast?
No fasting is required before this test. You may eat and drink normally on the day of collection. Always follow any specific instructions provided by your doctor.
Practical Tips Before Your Test
Keep the following points in mind before your appointment:
- Bring a detailed clinical history including your symptoms, previous test results, and family history, as this is required for the test
- Inform your doctor if you have had a blood transfusion in the past three months, as this may affect DNA quality
- Gather information about any family members with heart defects or upper-limb abnormalities before your appointment
- Consider genetic counselling before testing to understand what the results may mean for you and your family
Step-by-Step Procedure
The TBX5 full length gene sequence analysis (Holt-Oram syndrome) test procedure involves collecting one of several sample types depending on the clinical situation. The sample types required for this test are listed below:
- Peripheral Blood: A trained phlebotomist cleans the inside of your elbow and inserts a fine needle into a vein to collect a blood sample (3 ml) in a special EDTA tube.
- Chorionic Villus (CVS): For prenatal testing in the first trimester, a specialist collects a small amount of tissue (approximately 30 mg) from the placenta using chorionic villus sampling.
- Amniotic Fluid: For prenatal testing in the second trimester, a specialist collects amniotic fluid (the fluid surrounding the baby in the womb) through a procedure called amniocentesis.
- Cord Blood: In some cases, blood from the umbilical cord is collected at birth. This is handled by the delivering team and placed in a sterile container for dispatch.
- The sample is stored at 2 to 8°C and transported to a specialised genetics laboratory.
- The laboratory technician extracts your DNA and analyses the full TBX5 gene using Sanger sequencing.
- A molecular geneticist reviews the findings and prepares your clinical report.
Factors That Can Affect Accuracy
The following factors may influence the reliability of your results:
- Poor sample quality or incorrect storage during transport
- Recent blood transfusions, which can introduce another person's DNA into the sample
- Technical limitations of Sanger sequencing in detecting deep intronic variants (changes in non-coding regions of the gene)
- Absence of detailed clinical history or family information, which is needed to interpret results correctly
Understanding Your TBX5 Full Length Gene Sequence Analysis (Holt-Oram Syndrome) Test Results
Your doctor or genetic counsellor will review your results alongside your clinical history and symptoms. The table below outlines the possible outcomes:
| Result | Interpretation |
|---|---|
| No pathogenic variant detected | Normal result; no disease-causing TBX5 mutation found in the regions tested |
| Pathogenic or likely pathogenic variant detected | A mutation known or expected to cause Holt-Oram syndrome is present |
| Variant of uncertain significance (VUS) detected | Further clinical correlation or family studies are needed; periodic re-evaluation is recommended |
These ranges are general guidelines. Your doctor will interpret your results based on your age, health history, and other factors. Always consult a qualified healthcare professional for personalised medical advice.
Results During Special Conditions
The relationship between the specific TBX5 mutation found and the severity of physical symptoms is not always straightforward. Mutations that completely disable one copy of the gene (null alleles) typically cause significant abnormalities in both the limbs and the heart. Missense mutations (where one amino acid is swapped for another) may produce a range of outcomes: some lead to serious heart problems with only minor limb changes, while others cause more pronounced limb differences with less severe cardiac involvement.
How to Maintain Healthy Levels
If you or a family member receives a diagnosis of Holt-Oram syndrome, the following general steps are worth discussing with your doctor:
- Regular cardiac monitoring through echocardiography (heart ultrasound) and electrocardiography (ECG) helps track heart health over time
- Early physical therapy and support services can help children with limb differences reach their developmental potential
- First-degree relatives (parents, siblings, children) should undergo clinical evaluation even if they have no obvious symptoms, as severity can vary widely within families
Lupin Diagnostics TBX5 Full Length Gene Sequence Analysis (Holt-Oram Syndrome) Test Price
The TBX5 full length gene sequence analysis (Holt-Oram syndrome) test cost at Lupin Diagnostics starts at ₹24,000. This test requires a visit to a hospital; home collection is not available for this test. The table below shows indicative prices:
| City | Approximate Price (₹) |
|---|---|
| BHOPAL | 24000 |
| CHENNAI | 24000 |
| HYDERABAD | 24000 |
| KOLKATA | 24000 |
| NAVI MUMBAI | 24000 |
| PUNE | 24000 |
Prices are indicative and may vary by location. Please confirm the current price at the time of booking.
How to Book
Follow these steps for TBX5 full length gene sequence analysis (Holt-Oram syndrome) test online booking:
- Select the test on the Lupin Diagnostics website.
- Choose your city and preferred centre location.
- Visit the centre at your scheduled time for sample collection.
- Receive your report via email or WhatsApp within the stipulated turnaround time.
Frequently Asked Questions
Holt-Oram syndrome is a rare inherited condition that causes congenital heart defects and abnormalities in the upper limbs. It is caused by mutations in the TBX5 gene. The TBX5 full length gene sequence analysis (Holt-Oram syndrome) test confirms the genetic diagnosis, which helps with accurate family counselling and guides decisions about further testing for relatives.
This test is recommended for individuals who show upper-limb abnormalities alongside congenital heart defects, those with a confirmed family history of Holt-Oram syndrome, and family members of affected individuals who are seeking genetic counselling. Your doctor will assess whether the TBX5 full length gene sequence analysis (Holt-Oram syndrome) test is appropriate for your situation.
Among individuals who meet strict clinical criteria for Holt-Oram syndrome, a TBX5 mutation is identified in approximately 74% of cases. A negative result does not fully exclude the diagnosis, as some individuals with the condition do not show a detectable variant on current testing. Clinical findings and family history remain important alongside the genetic result.
The TBX5 full length gene sequence analysis (Holt-Oram syndrome) test can be performed on peripheral blood, chorionic villus (CVS), amniotic fluid, or cord blood. No fasting is required before sample collection. The choice of sample depends on whether the test is for a child or adult or for prenatal diagnosis.
No. A negative result reduces the likelihood of Holt-Oram syndrome but does not entirely exclude it. Some individuals who meet strict clinical criteria still test negative because certain mutations may occur in gene regions that standard sequencing does not cover. Your doctor will consider your overall clinical picture alongside the result.
Holt-Oram syndrome follows an autosomal dominant inheritance pattern, meaning each child of an affected parent has a 50% chance of inheriting the mutation. However, even within the same family, severity can vary considerably. Genetic counselling can help you understand what a positive result means for family planning.
Yes. For pregnancies where one parent carries a known TBX5 mutation, prenatal diagnosis is available using chorionic villus sampling in the first trimester or amniocentesis in the second trimester. These procedures are carried out by a specialist, and the samples are accepted for the TBX5 full length gene sequence analysis (Holt-Oram syndrome) test. Discuss the timing and risks of these procedures with your treating doctor.
TBX5 Full Length Gene Sequence Analysis (Holt-Oram Syndrome)
