A large screening of children in California helped to identify and distinguish a number of mutations likely to cause cystic fibrosis (CF) from mutations that are benign. The study, “Benign and Deleterious Cystic Fibrosis Transmembrane Conductance Regulator Mutations Identified by Sequencing in Positive Cystic Fibrosis Newborn Screen Children from California,” was published in the open access journal PLOS One.

Genetic mutations associated with CF are reported to reach more than 2,000, although only 200 of these defects are actually linked to disease risk. Now, a group of researchers at Children’s Hospital Los Angeles (CHLA) and the Genetic Disease Screening Program of the California Department of Public Health studied some of these uncategorized mutations to determine their link to cystic fibrosis.

Researchers performed a retrospective cohort study of children in California, screened from 2007 to 2011, then followed for two to six years. Newborns who tested positive for CF mutations were divided into three groups according to their genotype — those with two CF-causing mutations (CF-C), those with one mutation of varying clinic consequence (VCC), and those with one mutation of unknown disease liability (Unknown). Researchers assessed and compared each group profile for sweat chloride tests, pancreatic sufficiency status, and Pseudomonas aeruginosa colonization.

They concentrated on the latter two groups to better understand “the full spectrum of CFTR-related disease that may begin in early childhood,” the authors wrote in the study.

“Our study focused on children who have one CF-causing mutation and a second of varying or unknown clinical consequences … to see which mutations eventually resulted in disease symptoms and those that resulted in no disease,” Danieli B. Salinas, MD, from CHLA’s Division of Pulmonology and the study’s first author, said in a press release.

The team found that a small proportion of children with VCC and unknown CFTR mutations met the diagnostic criteria for CF. Specifically, 5% of those in the VCC group (4/78) and 11% of those classified as Unknown (27/244) developed the disease. The majority of the mutations were, however, benign. Children carrying Unknown mutations 2215insG with D836Y, and T1036N showed early and classical CF phenotype; those carrying 1525-42G>A, L320V, L967S, R170H, were benign, and these are most likely non-CF causing mutations.

“It is vital to determine and identify these mutations, because if we know the specific genetic mutation that causes the disease, we can possibly correct it,” said Dr. Salinas. Currently, there are drugs targeting specific mutations — nine different mutations, or about 4% of the CF population, is treatable with a drug called Kalydeco; Orkambi, another drug, is effective in about 70% of CF patients with a range of known mutations.

“If we know early, we can make a significant difference in the life of a child with CF,” Dr. Salinas concluded.