New gene associated with interstitial lung disease development in children
A previously unknown genetic cause of interstitial lung disease – in a puzzling case of a child – has been identified by researchers from Washington University School of Medicine, US. Interstitial lung disease is caused by scarring of the lung tissue that makes it increasingly difficult to breathe – some young patients develop the disease despite having no known genetic abnormalities.
In new research conducted as part of the National Institutes of Health’s (NIH) Undiagnosed Diseases Network, a team of specialists studied the lung tissue and genetic make-up of a 2-year-old child with interstitial lung disease. After painstaking analysis, they found a variant in a gene that makes a protein called RAB5B which plays a vital role in packaging lung surfactants into tiny compartments called vesicles and transporting them. The genetic variant caused the protein to be actively harmful.
[Surfactants are contained within the air sacs in the lungs. Surfactants keep the air sacs open and eases the exchange of oxygen and carbon dioxide during breathing. Many people with interstitial lung disease have been found to have abnormalities in the surfactant protein genes.]
The team confirmed this abnormality by studying the genetic variant in C. elegans roundworms: worms with one abnormal copy of the gene required three normal copies to restore normal function. The child had only one abnormal copy, thus demonstrating that even having one normal copy did not compensate for the poisonous protein produced by the mutated copy.
It was also found that neither of the child’s parents had the genetic abnormality, suggesting that the variant in the child’s DNA arose during embryonic development.
As explained by Dr. Jennifer A. Wambach, an associate professor of paediatrics, “This gene, RAB5B, is now associated with interstitial lung disease in children. There are patients with a clinical diagnosis of interstitial lung disease without a genetic explanation. For these patients, sequencing RAB5B may reveal changes in their DNA code that could account for their disease. Knowing the underlying genetic cause and identifying other patients with the same genetic problem can help us better predict the course of the disease, so we can better prepare patients and their families for what is to come, such as whether the patient may respond to treatments, or worsen to needing a lung transplant, or whether it may be appropriate to begin discussing compassionate care.”
While the diagnosis was not able to help the young patient in this case, knowledge of the underlying cause allowed the parents to know that the genetic variant was not inherited and there would be a very low chance of future children having the same disease.
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