The Q359K/T360K gene mutation, which is commonly found in Jewish patients of Georgian descent, is associated with a particularly severe cystic fibrosis (CF) phenotype, according to researchers.
Their study, “The Q359K/T360K mutation causes cystic fibrosis in Georgian Jews,” was published in the Journal of Cystic Fibrosis.
Cystic fibrosis is a chronic lung disorder that most frequently affects Caucasians. CF is a genetic disease and develops due to inherited mutations in the CFTR gene, which provides instructions to make the CFTR chloride channel protein.
Many mutations have been identified as causing CF, ranging from mild disease to severe phenotypes.
The Q359K/T360K mutation has previously been described in Jewish families from the former Soviet republic of Georgia. But there is a lack of clinical information regarding how this mutation causes CF, and the characteristic phenotype associated with it.
Researchers then set out to describe the clinical characteristics of patients who have this mutation.
Researchers analyzed the clinical records of patients with the Q359K/T360K mutation from three CF centers. They recorded various parameters of the disease, including maximal sweat chloride levels, FEV1 predicted levels (a measure used to assess lung function), sputum cultures (to identify bacterial colonization), and pancreatic insufficiency — a common condition in CF patients in which food is not properly digested due to a lack of digestive enzymes produced by the pancreas.
Nine Jewish patients of Georgian descent with the Q359K/T360K mutation were included in the study. The median age at CF diagnosis was 9.4, and ages ranged from infants just a few months old to 38 years. All patients had experienced pulmonary symptoms since early childhood.
Sweat chloride levels were significantly abnormal across all individuals, with a mean value of 106 meq/L. Normal sweat chloride levels are between 10 and 35 meq/L.
Nasal potential difference, which refers to a measure of the voltage across the nasal lining and reflects CFTR function, was performed in three patients. Similar to sweat chloride levels, all patients tested had abnormal values, suggesting impaired CFTR function.
When the data was collected, all patients were found to have a productive cough and bronchiectasis of variable severity. Additionally, the median FEV1 was 88%, ranging from 40% to 121% (values between 80% and 120% are considered normal).
Sputum cultures from the patients were found to be positive for a number of microorganisms typically found in CF patients, including Staphylococcus aureus, Achromobacter, Stenotrophomonas maltophilia, Aspergillus, and Pseudomonas aeruginosa.
Homozygous patients — which refers to patients who have two copies of the CF-causing mutation rather than just one — were also found to have pancreatic insufficiency.
The team concluded that in Jewish patients of Georgian descent, “the Q359K/T360K mutation resulted in a severe CF phenotype.”
To understand the effect of the mutation, researchers used a predictive algorithm to generate a computerized model of how the mutation affects CFTR function. Results indicated that the mutation likely interferes with chloride conductance through the CFTR channel.
Therefore, the team suggested that this group of patients “could possibly benefit from new therapies which improve CFTR conductance.”