Pulmonary Artery Hypertension (PAH) Panel

SEQmethod-seq-icon Our Sequence Analysis is based on a proprietary targeted sequencing method OS-Seq™ and offers panels targeted for genes associated with certain phenotypes. A standard way to analyze NGS data for finding the genetic cause for Mendelian disorders. Results in 21 days. DEL/DUPmethod-dup-icon Targeted Del/Dup (CNV) analysis is used to detect bigger disease causing deletions or duplications from the disease-associated genes. Results in 21 days. PLUSmethod-plus-icon Plus Analysis combines Sequence + Del/Dup (CNV) Analysis providing increased diagnostic yield in certain clinical conditions, where the underlying genetic defect may be detectable by either of the analysis methods. Results in 21 days.

Test code: CA0601

The Blueprint Genetics Pulmonary Artery Hypertension (PAH) Panel is an 11-gene test for genetic diagnostics of patients with clinical diagnosis an idiopathic or familial form of pulmonary hypertension. The panel covers also disorders affecting primarily the pulmonary capillaries or pulmonary veins.

Pulmonary hypertension and other disorders affecting the pulmonary circulation are inherited in an autosomal dominant and autosomal recessive manner. Genetic diagnosis may help classifying subtype of pulmonary hypertension. It can also give prognostic information that can be used in management decisions. Genetic diagnosis forms the basis for family screening and counseling.

About Pulmonary Artery Hypertension (PAH)

Pulmonary arterial hypertension (PAH) is characterized by widespread obstruction and obliteration of small pulmonary arteries leading to increased pulmonary vascular resistance, elevated pulmonary arterial pressure and eventually right ventricle failure and death. The clinical diagnosis of PAH can be established by the presence of mean pulmonary artery pressure >25 mmHg at rest or >30 mmHg during exercise when other known causes of pulmonary hypertension are excluded. Initial symptoms of pulmonary arterial hypertension are dyspnea (60%), fatigue (19%), syncope (8%), chest pain (7%), palpitation (5%), and edema (3%) and they correlate with the degree of RV failure. Mean age at diagnosis is 36 years but all age groups are involved. There is no cure for PAH and current medications form, for some patients, only a bridge to lung transplantation.

Availability

Results in 3-4 weeks. We do not offer a maternal cell contamination (MCC) test at the moment. We offer prenatal testing only for cases where the maternal cell contamination studies (MCC) are done by a local genetic laboratory. Read more.

Genes in the Pulmonary Artery Hypertension (PAH) Panel and their clinical significance
GeneAssociated phenotypesInheritanceClinVarHGMD
ACVRL1Hereditary hemorrhagic telangiectasiaAD31410
BMPR2Pulmonary hypertension, primary, Pulmonary venoocclusive diseaseAD49409
CAV1Partial lipodystrophy, congenital cataracts, and neurodegeneration syndrome, Lipodystrophy, congenital generalizedAD/AR710
EIF2AK4Pulmonary venoocclusive diseaseAR1132
ENGJuvenile polyposis syndrome, Hereditary hemorrhagic telangiectasiaAD33466
FOXF1Alveolar capillary dysplasia with misalignment of pulmonary veinsAD795
KCNA5Atrial fibrillationAD424
KCNK3Pulmonary artery hypertensionAD510
RASA1Parkes Weber syndrome, Capillary malformation-arteriovenous malformation, Spinal arteriovenous anomaliesAD18113
SMAD4Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, Polyposis, juvenile intestinal, Myhre dysplasia, Hereditary hemorrhagic telangiectasiaAD119128
TBX4AD326

Gene, refers to HGNC approved gene symbol; Inheritance to inheritance patterns such as autosomal dominant (AD), autosomal recessive (AR) and X-linked (XL); ClinVar, refers to a number of variants in the gene classified as pathogenic or likely pathogenic in ClinVar (http://www.ncbi.nlm.nih.gov/clinvar/); HGMD, refers to a number of variants with possible disease association in the gene listed in Human Gene Mutation Database (HGMD, http://www.hgmd.cf.ac.uk/ac/). The list of associated (gene specific) phenotypes are generated from CDG (http://research.nhgri.nih.gov/CGD/) or Orphanet (http://www.orpha.net/) databases.

Blueprint Genetics offers a comprehensive pulmonary artery hypertension (PAH) panel that covers classical genes associated with other secondary pulmonary hypertension, primary pulmonary hypertension, pulmonary heart disease, unspecified and pulmonary veno-occlusive disease. The genes are carefully selected based on the existing scientific evidence, our experience and most current mutation databases. Candidate genes are excluded from this first-line diagnostic test. The test does not recognise balanced translocations or complex inversions, and it may not detect low-level mosaicism. The test should not be used for analysis of sequence repeats or for diagnosis of disorders caused by mutations in the mitochondrial DNA.

Please see our latest validation report showing sensitivity and specificity for SNPs and indels, sequencing depth, % of the nucleotides reached at least 15x coverage etc. If the Panel is not present in the report, data will be published when the Panel becomes available for ordering. Analytical validation is a continuous process at Blueprint Genetics. Our mission is to improve the quality of the sequencing process and each modification is followed by our standardized validation process. All the Panels available for ordering have sensitivity and specificity higher than > 0.99 to detect single nucleotide polymorphisms and a high sensitivity for indels ranging 1-19 bp. The diagnostic yield varies substantially depending on the used assay, referring healthcare professional, hospital and country. Blueprint Genetics’ Plus Analysis (Seq+Del/Dup) maximizes the chance to find molecular genetic diagnosis for your patient although Sequence Analysis or Del/Dup Analysis may be cost-effective first line test if your patient’s phenotype is suggestive for a specific mutation profile. Detection limit for Del/Dup analysis varies through the genome from one to six exon Del/Dups depending on exon size, sequencing coverage and sequence content.

The sequencing data generated in our laboratory is analyzed with our proprietary data analysis and annotation pipeline, integrating state-of-the art algorithms and industry-standard software solutions. Incorporation of rigorous quality control steps throughout the workflow of the pipeline ensures the consistency, validity and accuracy of results. The highest relevance in the reported variants is achieved through elimination of false positive findings based on variability data for thousands of publicly available human reference sequences and validation against our in-house curated mutation database as well as the most current and relevant human mutation databases. Reference databases currently used are the 1000 Genomes Project (http://www.1000genomes.org), the NHLBI GO Exome Sequencing Project (ESP; http://evs.gs.washington.edu/EVS), the Exome Aggregation Consortium (ExAC; http://exac.broadinstitute.org), ClinVar database of genotype-phenotype associations (http://www.ncbi.nlm.nih.gov/clinvar) and the Human Gene Mutation Database (http://www.hgmd.cf.ac.uk). The consequence of variants in coding and splice regions are estimated using the following in silico variant prediction tools: SIFT (http://sift.jcvi.org), Polyphen (http://genetics.bwh.harvard.edu/pph2/), and Mutation Taster (http://www.mutationtaster.org).

Through our online ordering and statement reporting system, Nucleus, the customer can access specific details of the analysis of the patient. This includes coverage and quality specifications and other relevant information on the analysis. This represents our mission to build fully transparent diagnostics where the customer gains easy access to crucial details of the analysis process.

In addition to our cutting-edge patented sequencing technology and proprietary bioinformatics pipeline, we also provide the customers with the best-informed clinical report on the market. Clinical interpretation requires fundamental clinical and genetic understanding. At Blueprint Genetics our geneticists and clinicians, who together evaluate the results from the sequence analysis pipeline in the context of phenotype information provided in the requisition form, prepare the clinical statement. Our goal is to provide clinically meaningful statements that are understandable for all medical professionals, even without training in genetics.

Variants reported in the statement are always classified using the Blueprint Genetics Variant Classification Scheme modified from the ACMG guidelines (Richards et al. 2015), which has been developed by evaluating existing literature, databases and with thousands of clinical cases analyzed in our laboratory. Variant classification forms the corner stone of clinical interpretation and following patient management decisions. Our statement also includes allele frequencies in reference populations and in silico predictions. We also provide PubMed IDs to the articles or submission numbers to public databases that have been used in the interpretation of the detected variants. In our conclusion, we summarize all the existing information and provide our rationale for the classification of the variant.

A final component of the analysis is the Sanger confirmation of the variants classified as likely pathogenic or pathogenic. This does not only bring confidence to the results obtained by our NGS solution but establishes the mutation specific test for family members. Sanger sequencing is also used occasionally with other variants reported in the statement. In the case of variant of uncertain significance (VUS) we do not recommend risk stratification based on the genetic finding. Furthermore, in the case VUS we do not recommend use of genetic information in patient management or genetic counseling. For some cases Blueprint Genetics offers a special free of charge service to investigate the role of identified VUS.

We constantly follow genetic literature adapting new relevant information and findings to our diagnostics. Relevant novel discoveries can be rapidly translated and adopted into our diagnostics without delay. These processes ensure that our diagnostic panels and clinical statements remain the most up-to-date on the market.

Find more info in Support
Download PDF

Full service only

Choose an analysis method

$ $ 1400
$ $ 1000
$ $ 1600

Extra services

$ 500
Total $
Order now

ICD & CPT codes

CPT codes

SEQ81479
DEL/DUP81479


ICD codes

Commonly used ICD-10 codes when ordering the Pulmonary Artery Hypertension (PAH) Panel

ICD-10Disease
I27.0Primary pulmonary hypertension
I27.2Other secondary pulmonary hypertension
I28.9Pulmonary veno-occlusive disease
I27.9Pulmonary heart disease, unspecified

Accepted sample types

  • EDTA blood, min. 1 ml
  • Purified DNA, min. 5μg
  • Saliva (Oragene DNA OG-500 kit)

Label the sample tube with your patient’s name, date of birth and the date of sample collection.

Note that we do not accept DNA samples isolated from formalin-fixed paraffin-embedded (FFPE) tissue.