PulmoGene Panel (64 Genes) Test Details
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Background
The PulmoGene Panel contains 64 pulmonary disease genes that are associated with several defined hereditary syndromes, as well as non-syndromic presentations, including cystic lung disease, bronchiectasis, idiopathic pulmonary fibrosis, and pulmonary hypertension. The PulmoGene Panel uses a combination of next-generation sequencing technology and Sanger sequencing.
Read More...Available Pulmonary Disease Panel Tests
PulmoGene Panel - 64 genes
Gene Information
Read More for expanded gene table.
Read More...| Gene | Protein | OMIM# | Locus |
| ABCA3 | ATP-Binding Cassette, Sub-Family A (Abc1), Member 3 | 601615 | 16p13.3 |
| ACVRL1 | Activin A Receptor Type II-Like 1 | 601284 | 12q13.13 |
| AP3B1 | Adaptor-Related Protein Complex 3, Beta 1 Subunit | 603401 | 5q14.1 |
| ASCL1 | Achaete-Scute Complex Homolog 1 (Drosophila) | 100790 | 12q23.2 |
| BDNF | BDNF Antisense RNA | 611468 | 11p14.1 |
| BLOC1S3 | Biogenesis Of Lysosomal Organelles Complex-1, Subunit 3 | 609762 | 19q13.32 |
| BLOC1S6 | Biogenesis Of Lysosomal Organelles Complex-1, Subunit 6, Pallidin | 604310 | 15q21.1 |
| BMPR2 | Bone Morphogenetic Protein Receptor, Type Ii (Serine/Threonine Kinase) | 600799 | 2q33-q34 |
| 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 |
| CSF2RA | Colony Stimulating Factor 2 Receptor, Alpha, Low-Affinity (Granulocyte-Macrophage) | 306250 | Xp22.32 |
| CSF2RB | Granulocyte-Macrophage Colony-Stimulating Facotr Receptor, Beta | 138981 | 22q12.3 |
| 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 |
| DOCK8 | Dedicator Of Cytokinesis 8 | 611432 | 9p24.3 |
| DTNBP1 | Dystrobrevin-Binding Protein 1 | 607145 | 6p22.3 |
| EDN3 | Endothelin 3 | 131242 | 20q13.2-q13.3 |
| EFEMP2 | Egf Containing Fibulin-Like Extracellular Matrix Protein 2 | 604633 | 11q13.1 |
| ELMOD2 | Elmo/Ced-12 Domain Containing 2 | 610196 | 4q31.1 |
| ELN | Elastin | 130160 | 7q11.23 |
| ENG | Endoglin | 131195 | 9q34.11 |
| FBLN5 | Fibulin 5 | 604580 | 14q32.1 |
| FBN1 | Fibrilin 1 | 134797 | 15q21.1 |
| FLCN | Folliculin | 607273 | 17p11.2 |
| FOXF1 | Forkhead Box F1 | 601089 | 16q24.1 |
| GDNF | Glial Cell Derived Neurotrophic Factor | 600837 | 5p13.1-p12 |
| HPS1 | Hermansky-Pudlak Syndrome 1 | 604982 | 10q23.1-q23.3 |
| HPS3 | Hermansky-Pudlak Syndrome 3 | 606118 | 3q24 |
| HPS4 | Hermansky-Pudlak Syndrome 4 | 606682 | 22cen-q12.3 |
| HPS5 | Hermansky-Pudlak Syndrome 5 | 607521 | 11p14 |
| HPS6 | Hermansky-Pudlak Syndrome 6 | 607522 | 10q24.32 |
| HRAS | Harvey RAT Sarcoma Viral Oncogene Homolog | 190020 | 11p15.5 |
| LTBP4 | Latent Transforming Growth Factor Beta Binding Protein 4 | 604710 | 19q13.1-q13.2 |
| MUC5B | Mucin 5B, Oligomeric Mucus/Gel-Forming | 600770 | 11p15.5 |
| NF1 | Neurofibromin 1 | 613113 | 17q11.2 |
| NKX2.1 | NK2 Homeobox1 (Thyroid Transcription Factor 1) | 600635 | 14q13.2 |
| NME8 | NME/NM23 Family Member 8 | 607421 | 7p14.1 |
| PHOX2B | Paired-Like Homeobox 2B | 603851 | 4p12 |
| RET | RET Proto-Oncogene | 164761 | 10q11.2 |
| RPGR | Retinitis Pigmentosa GTPase Regulator | 312610 | Xp11.4 |
| 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 |
| SERPINA1 | Serpin Peptidase Inhibitor, Clade A (Alpha-1 Antiproteinase, Antitrypsin), Member 1 | 107400 | 14q32.1 |
| SFTPA1 | Surfactant Protein A1 | 178630 | 10q22.3 |
| SFTPA2 | Surfactant Protein A2 | 178642 | 10q22.3 |
| SFTPB | Surfactant Protein B | 178640 | 2p12-p11.2 |
| SFTPC | Surfactant Protein C | 178620 | 8p21 |
| SFTPD | Surfactant Protein D | 178635 | 10q22.2-q23.1 |
| SMAD9 | Smad Family Member 9 | 603295 | 13q12-q14 |
| STAT3 | Signal Transducer And Activator Of Transcription 3 (Acute-Phase Response Factor) | 102582 | 17q21.31 |
| TERC | Telomerase RNA Component | 602322 | 3q26 |
| TERT | Telomerase Reverse Transcriptase | 187270 | 5p15.33 |
| TSC1 | Tuberous Sclerosis 1 | 605284 | 9q34 |
| TSC2 | Tuberous Sclerosis 2 | 191092 | 16p13.3 |
Methodology
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 99.79% sensitive (482/483 variants tested; 95% CI = 98.86-99.96%) to detect variants changing a single base and 100.00% sensitive to detect insertion/deletions 1-21 bp in size (9/9 variants tested; 95% CI = 70.09-100.00%). 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 PulmoGene Panel remains unknown at this point.
References
Read More...Amato F, Bellia C, Cardillo G, Castaldo G, Ciaccio M, Elce A, Lembo F, Tomaiuolo R. 2012. Extensive molecular analysis of patients bearing CFTR-related disorders. J Mol Diagn. 14(1):81-9.
Armanios M. 2012. Telomerase and idiopathic pulmonary fibrosis. Mutat. Res. 730(1-2):52-8.
Boon M, Jorissen M, Proesmans M, De Boeck K. 2013. Primary ciliary dyskinesia, an orphan disease. Eur. J. Pediatr. 172(2):151-62.
Borie R, Kannengiesser C, Crestani B. 2012. Familial forms of nonspecific interstitial pneumonia/idiopathic pulmonary fibrosis: clinical course and genetic background. Curr Opin Pulm Med. 18(5):455-61.
De Pontual L, Trochet D, Caillat-Zucman S, Abou Shenab OA, Bougneres P, Crow Y, Cunningham S, Esteva B, Heberle LC, Leger J, Pinto G, Polak M, Shafik MH, Straus C, Trang H, Munnich A, Lyonnet S, Desguerre I, Amiel J. 2008. Delineation of late onset hypoventilation associated with hypothalamic dysfunction syndrome. Pediatr. Res. 64(6):689-94.
Hamvas A, Deterding RR, Wert SE, White FV, Dishop MK, Alfano DN, Halbower AC, Planer B, Stephan MJ, Uchida DA, Williames LD, Rosenfeld JA, Lebel RR, Young LR, Cole FS, Nogee LM. 2013. Heterogeneous pulmonary phenotypes associated with mutations in the thyroid transcription factor gene NKX2-1. Chest. 144(3):794-804.
Hu Q, Shifren A, Sens C, Choi J, Szabo Z, Starcher BC, Knutsen RH, Shipley JM, Davis EC, Mecham RP, Urban Z. 2010. Mechanisms of emphysema in autosomal dominant cutis laxa. Matrix Biol. 29(7):621-8.
Machado RD, Eickelberg O, Elliott CG, Geraci MW, Hanaoka M, Loyd JE, Newman JH, Phillips JA, Soubrier F, Trembath RC, Chung WK. 2009. Genetics and genomics of pulmonary arterial hypertension. J. Am. Coll. Cardiol. 54(1 Suppl):S32-42.
Muzykewicz DA, Sharma A, Muse V, Numis AL, Rajagopal J, Thiele EA. 2009. TSC1 and TSC2 mutations in patients with lymphangioleiomyomatosis and tuberous sclerosis complex. J. Med. Genet. 46(7):465-8.
Nickerson ML, Warren MB, Toro JR, Matrosova V, Glenn G, Turner ML, Duray P, Merino M, Choyke P, Pavlovich CP, Sharma N, Walther M, Munroe D, Hill R, Maher E, Greenberg C, Lerman MI, Linehan WM, Zbar B, Schmidt LS. 2002. Mutations in a novel gene lead to kidney tumors, lung wall defects, and benign tumors of the hair follicle in patients with the Birt-Hogg-Dubé syndrome. Cancer Cell. 2(2):157-64.
Nogee LM. 2010. Genetic Basis of Children's Interstitial Lung Disease. Pediatr Allergy Immunol Pulmonol. 23(1):15-24.
Pulkkinen V, Bruce S, Rintahaka J, Hodgson U, Laitinen T, Alenius H, Kinnula VL, Myllärniemi M, Matikainen S, Kere J. 2010. ELMOD2, a candidate gene for idiopathic pulmonary fibrosis, regulates antiviral responses. FASEB J. 24(4):1167-77.
Weese-Mayer DE, Berry-Kravis EM, Ceccherini I, Keens TG, Loghmanee DA, Trang H, sous-commission « syndrome d’hypoventilation alvéolaire centrale congénitale » de l’American Thoracic Society. 2013. [ATS clinical policy statement: Congenital central hypoventilation syndrome. Genetic basis, diagnosis and management]. Rev Mal Respir. 30(8):706-33.
Wei ML. 2006. Hermansky-Pudlak syndrome: a disease of protein trafficking and organelle function. Pigment Cell Res. 19(1):19-42.
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