27 January 2023
Gene mutation identified in PCD, rare disease
Published online 30 May 2018
A new genetic study improves understanding of the genetic basis of PCD making for more appropriate counselling of affected families.
Mucus has many benefits including trapping dirt particles and humidifying passageways. But too much of a good thing can lead to harm; in case of mucus, it’s a rare inherited genetic disease called primary ciliary dyskinesia (PCD).
“Our respiratory system––lungs, trachea, and inner ear––is lined with millions of hair-like cilia beating at 1,000 times a minute to clear the airways of mucus, inhaled particles and bacteria,” says Hannah Mitchison, a researcher at the Genetics and Genomic Medicine Programme at University College London. PCD affects the assembly and structure of this hair-like cilia. Its symptoms begin early in childhood.
Children affected by PCD accumulate mucus and have recurrent infections in the lung, leading to chronic productive cough, rhinosinusitis, bronchitis and pneumonia, glue ear, hearing loss and progressively declining lung function with breathing difficulties and even severe lung damage at later stages. Half the patients also suffer from left-right organ asymmetry, situs inversus, which causes congenital heart disease and can be associated with worse respiratory function.
Now, a new study1 has identified mutations in more than 36 different genes believed to cause PCD, accounting for disease in around 70% of PCD patients, according to Mitchison, co-author of the study.
Mitchison and fellow researchers, including from Egypt, used next-generation sequencing to locate mutations in a previously uncharacterised gene called C11orf70. Affected children showed mutations in C11orf70 that are associated with a loss of dyneins, the motors within the cilia that power its beating.
By identifying this gene, researchers can determine how the cilia movement, needed to clear the airways of the mucus, is impaired.
These findings can help diagnose more children affected sooner. As well, they “could help inform the identification of new gene-based therapies and targets for small molecule drug therapy in PCD,” says Mitchison.
- Fassad, M. R. et al. C11orf70 Mutations Disrupting the Intraflagellar Transport-Dependent Assembly of Multiple Axonemal Dyneins Cause Primary Ciliary Dyskinesia. The American Journal of Human Genetics. https://doi.org/10.1016/j.ajhg.2018.03.024 (2018)