Rare mutations in the CFTR gene — which is defective in patients with cystic fibrosis (CF) — may occur in specific ethnic groups, suggests a new study that urges wider screening of mutations in patients who test negative for most previously identified mutations linked to CF.
The study, “A rare CFTR mutation associated with severe disease progression in a 10‐year‐old Hispanic patient,” appeared in the journal Clinical Case Reports.
Mutations, or permanent alterations within the DNA sequence, in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene eventually produce a defective CFTR protein. This leads to the buildup of thick, sticky mucus which damages several organs, especially the lungs and pancreas.
CF incidence is particularly high in European whites and Ashkenazi Jews. However, authors noted, “a wide ethnic variation of CFTR mutations has been reported, indicating the need for diverse and ethnic‐specific mutations to be included in diagnostic and carrier screening conducted in the diverse U.S. population.”
In the present study, researchers report the case of a 10‐year‐old Hispanic boy diagnosed with CF at two months old, carrying two rare mutations in the Cftr gene, the c.233dupT and 7T/12TG. The first mutation identified in this boy (c.233dupT) completely blocked production of CFTR protein.
“The complete loss of this protein rather than merely a partial dysfunction as seen with many other mutations may help predict the mechanism of increased disease severity,” researchers wrote.
The 7T/12TG mutation, which this case represents only the second such reported case, was also predicted to influence disease course.
Previous studies in both U.S. Hispanics and African-Americans showed a pattern of population‐specific mutations that the standard mutation panel for CFTR used in screening cannot detect.
“In fact, the 23‐mutation panel (American College of Medical Genetics and Genomics) that is used for diagnosis and newborn screening in the general population detects fewer than half of the molecular mutations of patients with CF who are neither Caucasian nor Native American,” the team noted.
This case report adds to the findings of previous studies strengthening the necessity “for a broad range of CFTR mutation analyses or even full genotyping for patient populations who do not have their mutations identified with the standard mutation panels” the researchers concluded.
They adding: “This case also suggests a severe disease course associated with this particular mutation, for which early detection and treatment has the potential to improve outcomes.”