Pulmonary arterial hypertension (PAH) is caused by progressive narrowing of pulmonary arteries. This leads to increased pressure in the right side of the heart with symptoms including shortness of breath, chest pain, fatigue, palpitation, edema, and/or fainting. PAH may be associated with an underlying disease or environmental exposures, or may be otherwise classified as familial (with two or more affected relatives) or idiopathic (cause unknown and with negative family history).

The BMPR2 gene is a known contributor to PAH, with mutations detected in approximately 70% of familial and 11-40% of idiopathic cases. This gene encodes a receptor for specific proteins in the TGF-β superfamily of cell-signaling molecules that regulate the proliferation, differentiation, and apoptosis of pulmonary vascular cells. Mutations are dominantly-inherited, and penetrance is reduced with only approximately 20% of mutation carriers manifesting symptoms of PAH. Correlation of genotype with phenotype has not been found, as onset can vary by several decades within the same family and between unrelated individuals with the same mutation. Genetic anticipation, the increasingly earlier age of onset in subsequent generations, is found in some PAH families.

Genetic testing and genetic counseling should be offered to relatives of patients with familial PAH, and idiopathic PAH patients should be informed of the availability of these options for their relatives (American College of Chest Physicians Clinical Practice Guideline, 2007).

The Ambry Test: PAH AMPLIFIED includes concurrent full gene sequence analysis and gross deletion/duplication analysis of the BMPR2 gene. Results are reported together 14-28 days after testing is initiated. The Ambry Test: PAH Del/Dup analyzes only for gross deletions and duplications of the BMPR2 gene, which account for 5-20% of cases, and is for patients who have tested negative in previous gene sequencing.

Genetic testing is available to symptomatic patients and unaffected, at-risk relatives of patients according to the following guidelines.

Diagnostic testing for patients with known or suspected PAH: Pretest genetic counseling is recommended, and patient signature on the PAH Diagnostic Test Consent Form (in Materials, below) is required.

Carrier testing for at-risk relatives of PAH patients: As mutations causing approximately 30% of familial PAH are as yet undiscovered, Ambry’s testing for asymptomatic, at-risk relatives is limited to analysis for a disease-causing mutation that has, through prior testing, been detected in the affected relative(s). 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 PAH Carrier Test Consent Form (in Materials, below).

The Ambry Test: PAH AMPLIFIED
    (Abobe PDF document)

Pulmonary Arterial Hypertension Diagnostic Test Consent Form
   (required)
    (Abobe PDF document)

Pulmonary Arterial Hypertension Carrier Test Consent Form
   (required)
    (Abobe PDF document)

General Test Information
   The Ambry Test: PAH AMPLIFIED
    (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: PAH AMPLIFIED
83891, 83894, 83898, 83900, 83901, 83904, 83909, 83912

Ambry Test: PAH Deletion/Duplication Analysis
83891, 83894, 83900, 83901, 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.

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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: PAH AMPLIFIED analyzes the following types of mutations: nucleotide substitutions, small deletions, small insertions, small indels, gross deletions, and gross duplications. It is not intended to analyze the following types of mutations: gross insertions, gene 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: PAH AMPLIFIED is designed and validated to be capable of detecting ~99% of described BMPR2 mutations (considering ~1% to be the other types of mutations). Pulmonary arterial hypertension is a complex clinical disorder, which in some cases is due to alterations in the BMPR2 gene generally detected by the Ambry Test: PAH AMPLIFIED except as noted above. Mutations in other genes or the regions not tested by the Ambry Test: PAH AMPLIFIED can also give rise to clinical conditions similar or identical to PAH. 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.