Chronic Lung Disease, Pancreatic Insufficiency, and Infertility May Be Linked to CFTR Gene Mutations

Repeated lung infections that are extremely hard to cure? Unexplained pancreatic insufficiency or infertility? These diseases may seem unrelated, but in fact they may all be linked to CFTR gene mutations.

The CFTR gene is located at band 1 of region 3 on the long arm of human chromosome 7 (7q31), is about 250 kb long, contains 27 exons, and encodes the cystic fibrosis transmembrane conductance regulator (CFTR protein).

The CFTR gene is a vitally important functional gene in the human body. The CFTR protein it encodes functions mainly as a chloride channel on epithelial cell membranes, responsible for regulating the transmembrane transport of chloride and bicarbonate, thereby maintaining the balance of body fluids and electrolytes and affecting the viscosity of secretions such as mucus, sweat, and digestive juices.

More than 2,000 CFTR gene mutations have been discovered to date. According to their mechanism of effect on protein function, they are mainly divided into six classes: affecting protein synthesis (class I), affecting protein processing and trafficking (class II), affecting channel gating (class III), affecting channel conductance (class IV), reducing normal protein production (class V), and reducing protein stability (class VI). Among them, the F508del deletion mutation is the most common type, accounting for about 70% of mutations in patients worldwide.

When a mutation occurs in the CFTR gene, it causes impaired chloride transport, making airway mucus thick and prone to repeated pulmonary infections, and leading to cystic fibrosis.

The gold standard for diagnosing a CFTR gene mutation is CFTR genetic testing. Patients with clinical manifestations such as chronic lung disease, pancreatic insufficiency, or infertility (especially CBAVD (congenital bilateral absence of the vas deferens), or those with a family history, should consider CFTR genetic testing.

The test is performed by collecting peripheral blood and sequencing the entire CFTR gene sequence; detection of biallelic pathogenic mutations, combined with clinical manifestations, confirms a diagnosis of CF.

CFTR genetic testing can provide a basis for precision medicine. At present, CFTR protein modulators (such as ivacaftor) targeting specific mutation types (such as G551D) have been applied clinically; they can directly improve protein function and provide etiologically targeted precision treatment for patients. This is a contribution of molecular biology to modern medicine and also brings good news to such patients.