The discovery of a previously unknown gene variant suggests a rare respiratory illness may be more common among Inuit than previously thought. 

A study published last month in the Journal of Pediatric Pulmonology looks at the variant in a gene called DNAH11, which causes primary ciliary dyskinesia, or PCD.

PCD is a rare genetic disease affecting roughly one in every 10,000 to 40,000 people. It causes cilia, the microscopic hairs that line respiratory passages, to fail to move mucus out of the body. This traps bacteria and viruses in airways, leading to chronic infections and respiratory damage. 

People with PCD tend to suffer severe and recurrent lung infections like pneumonia, a chronic clogged and runny nose, and severe and recurrent ear infections. In about half of PCD cases, a person’s organs are reversed, such as the heart being on the right side of the body instead of the left. 

“Imagine the worst cold of your life — your head just felt so swollen like a water balloon, you couldn’t see straight, you couldn’t smell, you couldn’t taste, you’re choking or [have] secretions. That’s every day of life for a patient with PCD from birth,” said Dr. Adam Shapiro, an associate professor and a pediatric respirologist at McGill University’s Health Centre and one of the co-leads of the study.

Until recently, the way experts diagnosed PCD was by performing a biopsy from a place where you expect to find cilia, like the nose or the airways, and looking at the cilia under a microscope to see if it is moving abnormally or not at all.

But that method was never effective in diagnosing PCD among Inuit patients. 

“The cilia always look normal under the microscope, so the official word was Inuit don’t get PCD, period,” said Dr. Tom Kovesi said, a pediatric respirologist at the Children’s Hospital of Eastern Ontario in Ottawa and a professor of pediatrics at the University of Ottawa, who co-led the study with Shapiro.

The recent discovery of the variant in five people from Nunavut and two from Nunavik, however, indicates for the first time that PCD is present in the Inuit population of Canada. 

In 2019, Kovesi began working with a patient from Nunavut who exhibited many of the symptoms of PCD, but whose tests under microscope were coming back normal. 

But when Kovesi used genetic testing to determine what could be causing the symptoms, what came back “was a gene variant which was predicted to cause PCD [and] had never been found in any other population ever,” he said. 

After finding the same gene variant in other patients from Nunavut, Kovesi connected with Shapiro, who had been studying PCD for about 15 years in Quebec and, as it turned out, had also found the gene variant in two adult patients from Nunavik.

The discovery could be a sign PCD plays a role in recurrent pneumonia and chronic lung disease among Inuit.

“There’s a lot of reasons that lung disease in Inuit patients gets blamed on other things — aspiration [when food or liquid is breathed into the lungs], overcrowding, severe viral infections when you’re young,” Shaipro said, “but when you look closer, you see it really can’t be blamed on the psychosocial stuff. It’s in genetics, and none of us choose our genes.”

The next studies that will roll out will try to find out how common the gene variant actually is in Inuit through a process of genome sequencing in children with chronic lung disease, Shapiro said. 

That could shed some light on whether it plays a role in the high rates of other respiratory illnesses like tuberculosis in northern regions like Nunavut.

Anyone can get tuberculosis, Shapiro said, and social determinants of health, like housing and nutrition, do play a role in who is more vulnerable to it. 

But someone who has PCD will definitely experience damaged lungs, which would lead to more severe cases of TB or pneumonia. 

Now that scientists know what gene to look for when diagnosing PCD, the number of diagnoses among Inuit are growing. Researchers estimate that PCD could be as common among Inuit as one in 1,400, Shapiro said. 

“Politically, it argues very strongly for newborn screening to try and find this early in life, because most kids with this disease have to go through many pneumonias and hospitalizations and horrible ear infections and things like that before a doctor will think of this disease,” he said.

Treatments could include preventive measures like proper housing, better ventilation systems in homes, early immunizations and good nutrition, as well as antibiotics and chest physiotherapy, which helps move mucus inside the body.

“We’re just starting to pull on the thread, and the whole sweater can unravel,” Shapiro said.   

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