Bronchiectasis and Primary Ciliary Dyskinesia
Bronchiectasis is a chronic lung disease characterized by a pathologic and irreversible dilation of the airways.
Overview
Bronchiectasis is a chronic lung disease characterized by a pathologic and irreversible dilation of the airways. The heterogeneity of bronchiectasis is a major challenge in clinical practice. There are numerous underlying causes of bronchiectasis, although in many cases no cause is found. Known causes include post-infectious, aspiration syndromes, defects in host defence, cystic fibrosis, primary ciliary dyskinesia or even be systemic such as common variable immunodeficiency and anatomical defects including intraluminal airway obstruction, intramural obstruction or external airway compression. Bronchiectasis can be seen in all age groups, but the highest prevalence of disease is seen in the older age range (greater than 60) and women are disproportionately affected.
Primary Ciliary Dyskinesia (PCD) is a genetically and clinically heterogeneous disorder of motile cilia causing failure of mucociliary clearance and organ laterality defects and infertility inherited in an autosomal recessive pattern. It belongs to a rapidly expanding collection of disorders known as ciliopathies. Patients with primary ciliary dyskinesia have diverse clinical manifestations, including chronic upper and lower respiratory tract disease, left-right laterality defects, and infertility. A growing number of disease-associated genes and pathogenic mutations have been identified which encode ciliary structures that allow cilia to be functionally motile.
The Igenomix Bronchiectasis and Primary Ciliary Dyskinesia Precision Panel can be used as a diagnostic tool ultimately leading to a better management and prognosis of the disease. It provides a comprehensive analysis of the genes involved in this disease using next-generation sequencing (NGS) to fully understand the spectrum of relevant genes.
Indication
The Igenomix Bronchiectasis and Primary Ciliary Dyskinesia Precision Panel is indicated in those cases where there is a clinical suspicion or imaging findings with or without the following manifestations:
- Cough and daily mucopurulent sputum production
- Blood-streaked sputum
- Shortness of breath
- Pleuritic chest pain
- Wheezing
- Fever
- Weakness
- Fatigue
- Weight loss
- Infertility
- Recurrent upper and lower respiratory tract infections
- Situs inversus (organ laterality defects)
Clinical Utility
The clinical utility of this panel is:
- The genetic and molecular diagnosis for an accurate clinical diagnosis and improve prognosis.
- Early initiation of treatment with a multidisciplinary team in the form of prophylactic antibiotics, chest physiotherapy, bronchodilator therapy, and adjunctive surgical resection to improve symptoms, reduce complications and control exacerbations to reduce morbidity and mortality.
- Risk assessment and genetic counselling of asymptomatic family members according to the mode of inheritance.
Genes & Diseases
See all genes & diseases
Gene | OMIM Diseases | Inheritance* | % Gene Coverage (20x) | HGMD** |
ABCA3 | Idiopathic Pulmonary | AR | 100% | 286 of 289 |
ARHGEF1 | Immunodeficiency | AR | 90.23% | 2 of 2 |
ATM | Ataxia-telangiectasia | AD,AR | 99.93% | 1608 of 1632 |
ATP11A | IdiopathicPulmonary | – | 99.97% | NA of NA |
B2M | Familial Visceral | AD,AR | 100% | 4 of 4 |
BACH2 | Immunodeficiency | AD | 99.89% | 2 of 2 |
BLM | Bloom Syndrome | AR | 97.19% | 133 of 141 |
BLNK | AutosomalRecessive- | AR | 97.97% | 6 of 6 |
BTNL2 | Sarcoidosis | AD | 99.98% | 1 of 1 |
CARMIL2 | Immunodeficiency | AR | 96.16% | NA of NA |
CCDC103 | Primary Ciliary | AR | 99.92% | 6 of 6 |
CCDC39 | Primary Ciliary | AR | 99.56% | 48 of 52 |
CCDC40 | Primary Ciliary | AR | 98% | 50 of 50 |
CCDC65 | Primary Ciliary | AR | 99.98% | 3 of 3 |
CCNO | Primary Ciliary | AR | 99.94% | 12 of 12 |
CD19 | Common Variable | AD,AR | 99.99% | 7 of 7 |
CD79A | AutosomalRecessive- | AR | 99.99% | 8 of 8 |
CD79B | AutosomalRecessive- | AR | 100% | 3 of 3 |
CD81 | Common Variable | AR | 100% | 2 of 2 |
CD8A | Familial CD8 | AR | 99.60% | 1 of 1 |
CFAP221 | PrimaryCiliary- | – | 89.78% | NA of NA |
CFAP298 | Primary Ciliary | AR | na | na |
CFAP300 | Primary Ciliary | AR | na | na |
CFTR | Bronchiectasis, | AD,AR | 95.45% | 1615 of 1730 |
CLCA4 | Cystic Fibrosis | – | 97.66% | NA of NA |
CR2 | Common Variable | AD,AR | 99.92% | 19 of 19 |
CTLA4 | Autoimmune | AD | 99.97% | 60 of 60 |
CXCR4 | WhimSyndrome | AD | 100% | 19 of 19 |
DCTN4 | Cystic Fibrosis | – | 100% | 1 of 1 |
DNAAF1 | Primary Ciliary | AR | 99.55% | 36 of 37 |
DNAAF2 | Primary Ciliary | AR | 97.45% | 7 of 8 |
DNAAF3 | Primary Ciliary | AR | 98.95% | 13 of 14 |
DNAAF4 | Primary | AD,AR | 99.27% | NA of NA |
DNAAF5 | Primary Ciliary | AR | 89.27% | NA of NA |
DNAAF6 | Primary Ciliary | X,XR,G | 99.63% | NA of NA |
DNAH1 | Primary | AR | 100% | 58 of 58 |
DNAH11 | Primary Ciliary | AR | 99.27% | 159 of 169 |
DNAH17 | Spermatogenic- | AR | 99.99 | 12 of 12 |
DNAH5 | Primary Ciliary | AR | 100% | 277 of 278 |
DNAH8 | Primary Ciliary | – | 99.75% | 12 of 12 |
DNAH9 | Primary Ciliary | AR | 98.86% | 19 of 19 |
DNAI1 | Kartagener Syndrome, | AR | 96.91% | 43 of 43 |
DNAI2 | Primary Ciliary | AR | 98.89% | 8 of 8 |
DNAJB13 | Primary Ciliary | AR | 99.94% | 3 of 3 |
DNAL1 | Primary Ciliary | AR | 99.43% | 5 of 5 |
DNMT3B | Immunodeficiency- | AR | 100% | 59 of 59 |
DPP9 | IdiopathicPulmonary | – | 93.97% | 1 of 1 |
DRC1 | Primary Ciliary | AR | 100% | 9 of 9 |
DSP | IdiopathicPulmonary | AD,AR | 99.91% | 366 of 369 |
FAM13A | IdiopathicPulmonary | – | 99.91% | NA of NA |
FCGR2A | Cystic Fibrosis, | AD,AR | 93.97% | NA of NA |
FOXJ1 | Primary Ciliary | AD | 99.69% | 5 of 5 |
GAS2L2 | Primary Ciliary | AR | 89% | 4 of 5 |
GAS8 | Primary Ciliary | AR | 99.98% | 6 of 6 |
HLA-DRB1 | Diffuse Cutaneous | AD,MU | 97.19% | 2 of 2 |
HYDIN | Primary Ciliary | AR | 81.70% | 45 of 63 |
ICOS | Common Variable | AD,AR | 100% | 4 of 5 |
IGHM | AutosomalRecessive- | AR | 100% | NA of NA |
IGLL1 | AutosomalRecessive | AR | 100% | 2 of 2 |
IL21R | IL21R Immunodeficiency | AR | 99.97% | 10 of 10 |
IL6ST | Hyper-IgE Recurrent | AR | 99.34% | 2 of 2 |
IRF8 | Immunodeficiency 32A, | AD,AR | 100% | 9 of 9 |
IRF9 | Immunodeficiency, | AR | 100% | 5 of 5 |
LRBA | Common Variable | AR | 99.91% | 79 of 81 |
LRRC56 | Primary Ciliary | AR | 99.77% | 5 of 5 |
LRRC6 | Primary Ciliary | AR | 99.88% | 21 of 21 |
LRRC8A | AutosomalDominant- | AD | 100% | 2 of 2 |
MCIDAS | Primary Ciliary | AR | 99.92% | 4 of 4 |
MS4A1 | Common Variable | AR | 100% | 2 of 2 |
MUC5B | IdiopathicPulmonary | AD | 99.89% | 12 of 12 |
NBN | NijmegenBreakage- | AR,MU,P | 100% | 200 of 200 |
NCKAP1L | Immunodeficiency | AR | 100% | NA of NA |
NEK10 | Primary Ciliary | AR | 99.95% | 3 of 3 |
NFKB1 | Common Variable | AD | 99.98% | 38 of 41 |
NFKB2 | Common Variable | AD | 100% | 22 of 22 |
NME8 | Primary Ciliary | AR | 99.99% | 9 of 9 |
ODAD1 | Primary Ciliary | AR | 99.68% | 10 of 10 |
ODAD2 | Primary Ciliary | AR | 97.30% | 26 of 28 |
ODAD3 | Primary Ciliary | AR | 95% | 4 of 4 |
ODAD4 | Primary Ciliary | AR | na | na |
OFD1 | PrimaryCiliary- | X,XR,XD,G | 98.09% | NA of NA |
PARN | Idiopathic Pulmonary | AD,AR | 99.98% | 33 of 33 |
PGM3 | Immunodeficiency | AR | 99.99% | 17 of 17 |
PIK3CD | Combined | AD | 100% | 23 of 23 |
PIK3R1 | AutosomalRecessive- | AD,AR | 99.89% | 29 of 29 |
POLD1 | Mandibular Hypoplasia, | AD | 100% | 40 of 41 |
PRKCD | Autoimmune | AR | 100% | 9 of 9 |
RAC2 | Immunodeficiency | AD,AR | 100% | 5 of 5 |
RASGRP1 | Autoimmune | AR | 98.41% | 8 of 9 |
RIN2 | Macrocephaly, | AR | 99.60% | 4 of 4 |
RIPK1 | Autoinflammation | AD,AR | 98.03% | 12 of 14 |
RPGR | Primary Ciliary | X,XR,G | 94% | NA of NA |
RSPH1 | Primary Ciliary | AR | 100% | 10 of 10 |
RSPH3 | Primary Ciliary | AR | 99.85% | 5 of 5 |
RSPH4A | Primary Ciliary | AR | 99.98% | 27 of 27 |
RSPH9 | Primary Ciliary | AR | 100% | 13 of 13 |
RTEL1 | Dyskeratosis | AD,AR | 99.73% | 127 of 131 |
SCNN1A | Bronchiectasis | AD,AR | 99.95% | 46 of 46 |
SCNN1B | Idiopathic- | AD,AR | 100% | 56 of 56 |
SCNN1G | Bronchiectasis With | AD,AR | 100% | 28 of 28 |
SFTPA1 | Idiopathic | 100% | 4 of 4 | |
SFTPA2 | Idiopathic | AD | 99.98% | 6 of 6 |
SFTPC | Idiopathic | AD | 99.84% | 83 of 83 |
SLC29A3 | Histiocytosis- | AR | 100% | 32 of 32 |
SPAG1 | Primary Ciliary | AR | 94.80% | 11 of 12 |
SPEF2 | PrimaryCiliary | AR | 99.60% | 10 of 13 |
STAT1 | Autoimmune | AD,AR | 100% | 138 of 138 |
STK36 | PrimaryCiliary | – | 100% | 5 of 5 |
STN1 | IdiopathicPulmonary | AR | 99.87% | NA of NA |
STX1A | Cystic Fibrosis | – | 97% | 3 of 3 |
TAP1 | Bare Lymphocyte | AR | 100% | 7 of 7 |
TAP2 | Bare Lymphocyte | AR | 100% | 9 of 9 |
TAPBP | Bare Lymphocyte | AR | 93.99% | 1 of 1 |
TCF3 | AutosomalDominant | AD | 99.98% | 7 of 7 |
TERC | Dyskeratosis | AD | na | na |
TERT | Dyskeratosis Congenita, | AD,AR | 99.09% | 194 of 197 |
TGFB1 | Cystic Fibrosis, | AD,AR | 99.75% | 24 of 24 |
TNFRSF13B | Common Variable | AD,AR | 100% | 50 of 50 |
TNFRSF13C | Common Variable | AD,AR | 99.20% | 3 of 3 |
TNFSF12 | Common Variable | – | 95.06% | 1 of 1 |
TTC12 | Primary Ciliary | AR | 99.97% | NA of NA |
WDR1 | Periodic Fever, | AR | 100% | 9 of 9 |
ZMYND10 | Primary Ciliary | AR | 99.98% | 16 of 16 |
ZNF341 | Autosomal Recessive | AR | 100% | 6 of 6 |
* Inheritance: AD: Autosomal Dominant; AR: Autosomal Recessive; X: X linked; XLR: X linked Recessive; Mi: Mitochondrial; Mu: Multifactorial
** HGMD: Number of clinically relevant mutations according to HGMD
References
Flume, P. A., Chalmers, J. D., & Olivier, K. N. (2018). Advances in bronchiectasis: endotyping, genetics, microbiome, and disease heterogeneity. Lancet (London, England), 392(10150), 880–890. https://doi.org/10.1016/S0140-6736(18)31767-7
Bush, A., & Floto, R. A. (2019). Pathophysiology, causes and genetics of paediatric and adult bronchiectasis. Respirology (Carlton, Vic.), 24(11), 1053–1062. https://doi.org/10.1111/resp.13509
Nikolic A. (2018). Pathophysiology and Genetics of Bronchiectasis Unrelated to Cystic Fibrosis. Lung, 196(4), 383–392. https://doi.org/10.1007/s00408-018-0121-y
Knowles, M. R., Zariwala, M., & Leigh, M. (2016). Primary Ciliary Dyskinesia. Clinics in chest medicine, 37(3), 449–461. https://doi.org/10.1016/j.ccm.2016.04.008
Editorial, A. (2018). Adult patients with bronchiectasis: clinical guideline of European Respiratory Society. Russian Pulmonology, 28(2), 147-168. doi: 10.18093/0869-0189-2018-28-2-147-168
Lucas, J. S., Davis, S. D., Omran, H., & Shoemark, A. (2020). Primary ciliary dyskinesia in the genomics age. The Lancet. Respiratory medicine, 8(2), 202–216. https://doi.org/10.1016/S2213-2600(19)30374-1
Horani, A., & Ferkol, T. W. (2018). Advances in the Genetics of Primary Ciliary Dyskinesia: Clinical Implications. Chest, 154(3), 645–652. https://doi.org/10.1016/j.chest.2018.05.007
