Exploring A Lung Disease So Rare There Are Only 7 Diagnoses: NEK10 Case Study

When the 31-year-old woman showed up to Massachusetts General Hospital with a nasty respiratory infection, she was somewhat used to it. In fact, she had been plagued with respiratory problems throughout her entire life. But on this particular visit, she discovered she’d need a double lung transplant. Genetic testing unlocked the key to her mysterious and rare lung disease: a mutated NEK10 gene. Find the full case study from MIT’s Whitehead Institute.

The Case Study

Respiratory Issues

When the woman was a baby, her respiratory struggles began. First, she would come down with a fever. Next, she developed a severe, persistent, and mucus-laced cough. As an adult, the bronchi in her lungs were swollen, worsening her issues.

Her airways were full of mucus. In some cases, mucus is a positive. It stops dirt, bacteria, and other foreign substances from entering into our lungs and harming us. In normal situations, the foreign substances get stuck on the mucus, and cilia (small organelles) force it out of our bodies. However, in this patient’s case, the mucus was too thick. The body could not get rid of it.

Potential Conditions

Doctors considered that the woman could be experiencing one of two conditions:

  • Cystic fibrosis – Cystic fibrosis is a progressive condition causing digestive system and respiratory damage. People with cystic fibrosis create thick, sticky, heavy mucus, which accumulates in their body. This can make it more difficult to breathe, lead to frequent infections, and damage the organs. Symptoms include constipation, frequent lung infections, persistent coughing, shortness of breath, and difficulty gaining weight. Learn more about cystic fibrosis.
  • Bronchiectasis – Bronchiectasis is a lung condition in which someone’s bronchial tubes are damaged, thickened, or widened. In this condition, mucus collects in the lungs. It can affect one or multiple sections of the lungs. Bronchiectasis causes include cystic fibrosis, HIV, inflammatory bowel disease, and autoimmune disorders. Symptoms include a chronic cough, wheezing, chest pain, frequent respiratory infections, and weight loss. Learn more about bronchiectasis.

However, testing for both was negative.

Uncovering a New Lung Disease

Dr. Raghu Chivukula, whose medical focus was rare lung diseases, became committed to studying the woman’s case. He partnered with the Pathways Consult Service, a program from Massachusetts General Hospital designed to solve medical mysteries.

To start, the woman was asked about her medical history and prior experiences. Doctors also spoke to the woman’s family. This ended up being crucial; her siblings also showed respiratory symptoms, and an interview found that their family frequently experienced respiratory issues. Chivukula knew what needed to happen next: genetic testing.

The NIH defines genetic testing as:

a type of medical test that identifies changes in chromosomes, genes, or proteins. The results of a genetic test can confirm or rule out a suspected genetic condition or help determine a person’s chance of developing or passing on a genetic disorder.


Researchers found a novel gene mutation in NEK10 that was present in the genetic information provided by the woman and her family. NEK10 codes for a signaling protein. Prior studies show that NEK10 may play a role in the intersection between DNA damage and cancer. However, no prior studies have ever linked NEK10 and respiratory issues.

Dr. Chivukula began his research within MIT’s Whitehead Institute. Genetic testing also showed that the woman’s genetic mutation added 7 amino acids into the NEK10 protein.

Six Other Patients

By sourcing data from other hospitals, Dr. Chivukula found 6 other patients with NEK10 mutations that changed the amount of amino acids. All patients with this mutation experienced respiratory inflammation and excess mucus in the respiratory tract. But what was causing this lung disease?

Further Studying this Novel Lung Disease

Dr. Chivukula took the woman’s respiratory tissue (following her lung transplant), and also sourced healthy tissue from other individuals. Genetic testing was performed using messenger RNA (mRNA). He found that, compared to undifferentiated lung stem cells, tissue from the patient had heightened levels of NEK10 mRNA.

Researchers wondered if they could replicate these results in cultured tissues. They created a thin film that was reminiscent of respiratory lining, on which cells grew. The results were similar: more NEK10 mRNA. As a result, researchers determined that NEK10 was most active in airway cells.

Next, they added fluorescence to the cells. Healthy cells turned red, while unhealthy cells turned green. Researchers found that cells covered in cilia were turning green at a much higher rate than other cells. Thus, the woman was diagnosed with a novel form of ciliopathy, a condition marked by the abnormal use or damage of cilia.

Finally, Dr. Chivukula closely examined the woman’s cilia. He found that the NEK10 mutation caused her cilia not to develop properly. Ultimately, this meant that the cilia were ineffective in removing mucus from the airways. Throughout the years, mucus continued to accumulate. But on top of that, her airways became more and more inflamed. After examining the woman and the other 6 patients, the researchers determined that the genetic issue must be present in both gene copies. They hope to continue researching this unique lung disease moving forward.

You can find the full findings in Nature Medicine.

Jessica Lynn

Jessica Lynn

Jessica Lynn has an educational background in writing and marketing. She firmly believes in the power of writing in amplifying voices, and looks forward to doing so for the rare disease community.

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