Bronchiectasis Panel (17 Genes) Test Details
The Bronchiectasis Panel sequences 17 genes associated with hereditary lung diseases that cause localized, irreversible dilation of the bronchi, and obstructive lung disease. When naturally occurring mucus in the respiratory airway cannot be cleared, bacteria develop and cause repeated respiratory infections that result in severe and irreversible damage to the lungs. Hereditary lung diseases identified by variants in these genes include cystic fibrosis and primary ciliary dyskinesia.
Bronchiectasis - SCNN1A, SCNN1B, SCNN1G
Cystic fibrosis (CF) - CFTR
Primary ciliary dyskinesia (PCD) & Bronchiectasis - CCDC39, CCDC40, DNAAF1, DNAAF2, DNAH11, DNAH5, DNAI1, DNAI2, DNAL1, NME8, RSPH1, RSPH4A, RSPH9
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|CCDC39||Coiled-Coil Domain Containing 39||613798||3q26.33|
|CCDC40||Coiled-Coil Domain Containing 40||613799||17q25.3|
|CFTR||Cystic Fibrosis Transmembrane Conductance Regulator||602421||7q31.2|
|DNAAF1||Dynein, Axonemal, Assembly Factor 1||613190||16q24.1|
|DNAAF2||Dynein, Axonemal, Assembly Factor 2||612517||14q21.3|
|DNAH11||Dynein, Axonemal, Heavy Chain 11||603339||7p21|
|DNAH5||Dynein, Axonemal, Heavy Chain 5||603335||5p15.2|
|DNAI1||Dynein, Axonemal, Intermediate Chain 1||604366||9p13.3|
|DNAI2||Dynein, Axonemal, Intermediate Chain 2||605483||17q25|
|DNAL1||Dynein, Axonemal, Light Chain 1||610062||14q24.3|
|NME8||Nme/Nm23 Family Member 8||607421||7p14.1|
|RSPH1||Radial Spoke Head 1 Homolog (Chlamydomonas)||609314||21q22.3|
|RSPH4A||Radial Spoke Head 4 Homolog A (Chlamydomonas)||612647||6q22.1|
|RSPH9||Radial Spoke Head 9 Homolog (Chlamydomonas)||612648||6p21.1|
|SCNN1A||Sodium Channel, Nonvoltage-Gated 1 Alpha||600228||12p13|
|SCNN1B||Sodium Channel, Nonvoltage-Gated 1, Beta||600760||16p12.2-p12.1|
|SCNN1G||Sodium Channel, Nonvoltage-Gated 1, Gamma||600761||16p12|
The Bronchiectasis Panel should be ordered for individuals with a diagnosis or suspected diagnosis of bronchiectasis, including primary ciliary dyskinesia (PCD), cystic fibrosis (CF), Kartagener syndrome. This panel will provide comprehensive coverage of the implicated genes and minimize the incidence of variants of unknown significance compared with the PulmoGene panel.
We recommend careful consideration when deciding whether to order the full panel or the disease-specific sub-panels. For clinically complex cases where the diagnosis is not clear, the complete multi-disease panel may shorten the “testing odyssey.” However, it should be noted that large multi-disease panels typically come with an increased risk of an inconclusive result, as many genes have not yet been sufficiently interrogated for all included diseases. Disease-specific sub-panels may, therefore be the better first line test for individuals with clear clinical diagnoses.
Please note: As per current American Congress of Obstetricians and Gynecologists’ guidelines, this test is not recommended as a routine carrier screen for individuals with cystic fibrosis, as it may yield inclusive results (Obstet Gynecol. 2011 Apr;117(4):1028-31).
This test is performed by next-generation sequencing, using Agilent SureSelect capture, followed by sequencing of the coding regions and splice sites, using Illumina sequencing technologies. Variant calls are generated, using the Burrows-Wheeler Aligner, followed by Genomic Analysis Tool Kit (GATK) analysis. Detection of copy number variants (CNVs) encompassing 1 or more exons is performed, using VisCap™ analysis. Sanger sequencing is used to fill in regions with insufficient coverage. All clinically significant variants are confirmed by Sanger sequencing or droplet digital PCR. Variants classified as likely benign or benign are not confirmed. This test does not detect variants in non-coding regions that could affect gene expression, aside from the splice junctions, and a few exons have been excluded due to technical difficulties. CNV analysis is performed only when data meets necessary quality standards and may not be available for all cases.
Analytical and Clinical Sensitivity
This test is 100.00% sensitive (525/525 variants tested; 95% CI = 99.27-100.00% ) to detect variants changing a single base and 100.00% sensitive to detect insertion/deletions 1-21 bp in size (17/17 variants tested; 95% CI = 81.57-100.00%). Regions with high sequence homology are included in this test if a unique Sanger sequencing assay can be designed to rule out false positive calls. Analytical sensitivity in these regions may be reduced.
Given the recent launch of this disease area, the detection rate for the Bronchiectasis Panel remains unknown at this point.
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