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 and 5 million worldwide. More information about the presentation and course of the disease is available below. Most cases of IPF are sporadic (occurring in just one member of a family), while 2-20% of cases are familial.

Recent research has yielded specific insights into the genetic causes of IPF. In two new studies, mutations in the TERT and TERC genes accounted for approximately 10% of familial cases and a low percentage of sporadic IPF. 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. Fibrosis in IPF patients with these mutations is thought to occur after premature alveolar epithelial cell death due to failed restoration of telomere length.

The Ambry Test is concurrent full gene sequence analyses of the TERT and TERC genes. Results are reported together 10-21 days after testing is initiated. Pretest genetic counseling is recommended, and patient signature on the IPF Diagnostic Test Consent Form (in Materials, below) is required.

Genetic testing is available to patients who are suspected or known to have interstitial lung disease. A result positive for a previously described mutation confirms the genetic cause of IPF. A negative result does not definitively rule out the presence of a heritable IPF mutation because there are other genes yet to be identified or characterized that may cause IPF. 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.

Idiopathic pulmonary fibrosis is one of over 200 interstitial lung diseases. The term idiopathic refers to its unknown cause. Patients typically present after age 50 with chronic cough, shortness of breath, and inspiratory crackles. Familial and sporadic cases are indistiguishable except that familial cases may present up to a decade earlier. Pulmonary function declines quickly to pulmonary failure over 3-5 years following diagnosis and lung transplant is the only clearly effective life-extending treatment option.

Diagnosis is based on a combination of results from pulmonary function tests, high resolution CT which reveals bilateral reticular opacities and cystic honeycomb changes, and biopsy findings of usual interstitial pneumonitis (UIP). Fibrosis occurs in foci of connective tissue and fibroblast overgrowth that suggest a pattern of recurrent injury and abnormal repair. Knowledge of telomerase’s role in maintaining cell viability and discovery of its direct involvement in IPF can focus drug development efforts on preventing alveolar cell death and controlling repair responses.

The Ambry Test: IPF Telomerase
    (Abobe PDF document)

Idiopathic Pulmonary Fibrosis Diagnostic Test Consent Form (required)
    (Abobe PDF document)

General Test Information
   The Ambry Test: IPF Telomerase (TERC)
    (Abobe PDF document)

General Test Information
   The Ambry Test: IPF Telomerase (TERT)
    (Abobe PDF document)

The following CPT Codes for The Ambry Test reflects Ambry Genetics’ interpretation of CPT coding requirements based on AMA guidelines:

Ambry Test: IPF Telomerase
83891, 83894, 83898, 83904, 83909, 83912

CPT codes are provided only as a guide to assist you in billing. CPT coding is the sole responsibility of the billing party.

Disclaimer:

This test was developed and its performance characteristics were determined by Ambry Genetics Corporation. The laboratory is regulated under the Clinical Laboratory Improvement Amendments 2003 as qualified to perform nonwaived testing. The Ambry Test: IPF Telomerase analyzes the following types of mutations: nucleotide substitutions, small deletions, small insertions, and small indels. It is not intended to analyze the following types of mutations: gross insertions, gross rearrangements, deep intronic variations, and other unknown abnormalities. The pattern of mutation types varies with the gene tested and the Ambry Test detects a high but variable percentage of known and unknown mutants of the classes stated. A negative result from the analysis cannot rule out the possibility that the tested individual carries a rare unexamined mutation or mutation in the undetectable group. The Ambry Test: IPF Telomerase is designed and validated to be capable of detecting ~99% of all described TERT mutations, ~99% of TERC mutations described in IPF (considering ~1% to be the undetected types of mutations), and ~90% of all described TERC mutations. Idiopathic pulmonary fibrosis is a complex clinical disorder, which in some cases is due to alterations in the TERT or TERC genes generally detected by the The Ambry Test: IPF Telomerase except as noted above. Mutations in other genes or the regions not tested by the Ambry Test: IPF Telomerase can also give rise to clinical conditions similar or identical to IPF. Although molecular tests are highly accurate, rare diagnostic errors may occur. Possible diagnostic errors include sample mix-up, erroneous paternity identification, technical errors, and genotyping errors. Genotyping errors can result from trace contamination of PCR reactions, from maternal cell contamination in fetal samples, from rare genetic variants, which interfere with analysis, or from other sources. This report does not represent medical advice. Any questions, suggestions, or concerns regarding interpretation of results should be forwarded to a genetic counselor, medical geneticist, or physician skilled in interpretation of the relevant medical literature. References are available upon request.