Researchers found a new defect called the R248G mutation in the CFTR gene in three Spanish siblings whose diagnoses indicate borderline cystic fibrosis, and suggest a possible link between this defect, pancreatitis (inflammation of the pancreas), and infertility.
The findings were reported in the article “R248G cystic fibrosis transmembrane conductance regulator mutation in three siblings presenting with recurrent acute pancreatitis and reproductive issues: a case series,” in the Journal of Medical Case Reports.
The CFTR (cystic fibrosis transmembrane conductance regulator) protein is present in cells lining the lungs, pancreas, gastrointestinal tract, and reproductive system. Different defects in the CFTR gene, which encodes the CFTR protein, are known to cause cystic fibrosis and related disorders.
CFTR gene mutations are also known to be linked to decreased lung function; bacteria infection — especially Pseudomonas aeruginosa and Staphylococcus aureus; pancreatic insufficiency (a malfunction in the pancreas, an organ important for digestion); and male infertility, due to defects, on one or both sides of the body, of the vas deferens, a channel that helps transport sperm.
None of the three siblings who had the new R248G mutation in the CFTR gene had decreasing lung function, but two of them had S. aureus present in their bodies. Their diagnoses indicated borderline cystic fibrosis.
The brother in the sibling group was a 39-year-old infertile man who lacked the vas deferens on one side since birth and had repeated bouts of stomach pain. The middle sibling was a 32-year-old woman with periods of infertility, two miscarriages, repeated bouts of stomach pain, and recurrent pancreatitis. The youngest sibling was a 29-year-old woman with repeated bouts of pancreatitis and stomach pain.
Researchers suspected that the newly discovered R248G mutation was the cause of the lack of the vas deferens in the brother, the decreased fertility in the 32-year-old sister, and pancreatitis in both sisters.
All three siblings also had another mutation in the CFTR gene called N1303K. This better-known mutation usually does not cause problems in fertility or in the pancreas when it is only present in one copy of the CFTR gene (each person inherits one copy from their father and one from their mother).
“We suggest that the R248G mutation may be associated with the recurrent acute pancreatitis exhibited by [the sisters] because it is unlikely that the N1303K … mutation is the underlying molecular cause when taking into consideration that each patient has only one copy of this mutant allele,” the research team wrote.
“The recurrent episodes of epigastric pain and heartburn observed in [the brother and older sister] could be symptomatically masking the clinical signs of recurrent acute pancreatitis,” they added.
Based on these case reports, the team concluded that the new R248G CFTR mutation is linked to congenital unilateral absence of the vas deferens in males, reduced female fertility, and recurrent acute pancreatitis. The authors emphasized that future studies should investigate the impact of the R248G mutation.