Idiopathic Pulmonary Fibrosis (IPF Telomerase)
Idiopathic Pulmonary Fibrosis (IPF) is a severe disease of lung scarring and progressive shortness of breath that affects about 128,000 people in the United States, and 1 in 5 million people worldwide.
PrintIdiopathic Pulmonary Fibrosis (IPF) is a severe disease of lung scarring and progressive shortness of breath that affects about 128,000 people in the United States, and 1 in 5 million people worldwide.
Most cases of IPF are sporadic, while 2-20% of cases are familial, inherited in an autosomal dominant pattern with incomplete penetrance. Onset may be 10-12 years earlier in familial Pulmonary Fibrosis cases, but the expected course of disease is the same.
Mutations in telomerase TERT and TERC genes account for approximately 10% of familial IPF cases and a low percentage of sporadic IPF. The Ambry Test: IPF Telomerase includes concurrent Gene Sequence Analysis of both the TERT and TERC genes.
Genetic testing is available to symptomatic patients and unaffected, at-risk relatives of patients according to the counseling and consent guidelines described on the linked Test Information Sheet. Signatures on either the IPF Diagnostic Test Consent Form or IPF Carrier Test Consent Form are required.
Idiopathic pulmonary fibrosis (IPF) is a severe disease of lung scarring and progressive shortness of breath that affects about 128,000 people in the U.S.1 and 5 million worldwide.2 Patients typically present after age 50 with chronic cough, inspiratory crackles, usual interstitial pneumonitis (UIP) on histology, and bibasilar reticular opacities with cystic honeycomb changes on radiography. Most cases of IPF are sporadic (occurring in just one member of a family), while 2-20% of cases are familial, inherited in an autosomal dominant pattern with incomplete penetrance.3 Onset may be 10-12 years earlier in familial cases, but the expected course of disease is the same.4
Recent research shows mutations in telomerase TERT and TERC genes account for approximately 10% of familial IPF cases and a low percentage of sporadic IPF.3,4 These two genes encode components of telomerase, an enzyme that elongates telomeres to maintain chromosome integrity after a normal loss of nucleotides during cell division. Mutations are associated with shortened telomeres and most cause reduced or absent telomerase activity.3,4 Fibrosis in IPF patients is thought to occur after premature alveolar epithelial cell death due to failed restoration of telomere length.
Diagnostic testing for patients with known or suspected IPF:
Genetic testing is available to patients who are suspected or known to have an interstitial lung disease. In patients positive for a previously described mutation, the cause of IPF is confirmed and appropriate surveillance may begin or continue for siblings and offspring. Negative results are highly reliable in ruling out TERT and TERC mutations, but they cannot rule out the presence of all heritable IPF mutations because there may be other causative genes not yet identified. Patients with a negative result, especially those with family history of IPF, are encouraged to follow genetics developments and consider involvement in research. Referrals to qualified studies and support organizations are available from Ambry Genetics. The patient’s signature on the IPF Diagnostic Test Consent Form is required.
Carrier testing for at-risk relatives of IPF patients:
As it is still the minority of IPF families that will have detectable mutations, testing for asymptomatic atrisk relatives is limited to analysis for a disease-causing mutation that has been detected in the affected relative(s) through prior testing. Please call an Ambry Genetics counselor for assistance in arranging family member or carrier testing. Pretest genetic counseling by a genetics professional or the patient’s physician is required, as are signatures of this professional and the patient on the IPF Carrier Test Consent Form.
The Ambry Test: IPF Telomerase includes concurrent sequence analyses of the TERT and TERC genes. PCR-based double-stranded automated sequencing is performed in the sense and antisense directions for exons 1-16 of the TERT gene, plus at least 20 bases into the 5’ and 3’ ends of all the introns, and for the entire single-exon TERC gene. Specific mutation analysis for individual TERT or TERC mutations known to be in the family is also available.
Mutations in TERT or TERC detectable by this test are found in about 10% of familial pulmonary fibrosis and a low percentage of sporadic cases. This test is designed to detect ~99% of all described TERT mutations. It is designed to detect ~99% of TERC mutations associated with IPF and ~90% of all described TERC mutations; some TERC mutations not associated with isolated pulmonary fibrosis are not detected by this test.
Blood: Collect 3-5 cc from adult or 2 cc minimum from child into EDTA purple-top tube (first choice) or ACD yellow-top tube (second choice). Store at room temperature or refrigerate. Ship at room temperature.
Blood Spot: Minimum of one complete spot approximately 0.5 inch in diameter on S&S 903 collection paper or similar. Store in a clean plastic bag at room temperature. Ship at room temperature.
Saliva: Collect 2 ml into Oragene™ DNA Self Collection container. Store and ship at room temperature.
DNA: Minimum DNA Amount of 5μg of DNA at a concentration of ~100ng/μl in 50μl TE (10mM Tris-Cl pH 8.0, 1mM EDTA); preferred 20μg. Store frozen and ship on ice or dry ice. A signed IPF Diagnostic Test Consent Form or IPF Carrier Test Consent Form is required for testing.
| Technique | Days |
|---|---|
| IPF Telomerase (TERT, TERC) | 10-21 |
1. Coalition for Pulmonary Fibrosis website. Available at: click here. Accessed May 8, 2008.
2. Meltzer EB and Noble PW. Idiopathic pulmonary fibrosis. Orphanet J Rare Dis. 2008;26:3:8. [PMID: 18366757]
3. Armanios MY et al. Telomerase mutations in families with idiopathic pulmonary fibrosis. N Engl J Med. 2007;356:1317-1326. [PMID: 17392301]
4. Tsakiri KD et al. Adult-onset pulmonary fibrosis caused by mutations in telomerase. Proc Nat Acad Sci. 2007;104;7552-7557. [PMID: 17460043]