Cystic Fibrosis Genotyping Study Reveals Discrepancies in Mutations Screening for White and Nonwhite CF Patients

Cystic Fibrosis Genotyping Study Reveals Discrepancies in Mutations Screening for White and Nonwhite CF Patients

In a new study, researchers from the Stanford University correlate the later stage cystic fibrosis (CF) diagnosis seen in nonwhite patients with the fact that most widely used CF newborn screening panels do not screen sufficiently for the variants most seen in nonwhite ethnic groups. The research paper, entitled “Cystic Fibrosis: A Review of Associated Phenotypes, Use of Molecular Diagnostic Approaches, Genetic Characteristics, Progress, and Dilemmas,” was published in The Journal of Molecular Diagnostics.

Researchers examined CF transmembrane conductance regulator (CFTR) genotyping data of CF patients from the CF Foundation Patient Registry. The research included people from different ethnicities, non-Hispanic whites (22,206), Hispanics (1,955), blacks (1,214), Asians (156), and Native Americans (171). Analysis of results showed that 90% of white patients and 83% of Native American patients have a particular CF mutation, the p.Phe508del, and half of these patients have two copies of this mutation. On the other hand, the scientists found that 30% of Hispanics, 38% of blacks, and 41% of Asians did not possess the mutation at all, and the likelihood of these ethnic groups carrying two copies of the mutation was also lower. Dr Iris Schrijver, MD and Professor at the Stanford University commented on these results in a press release, “Our results confirm the widely held notion that the American College of Medical Genetics and Genomics list of 23 mutations that was specifically designed for carrier screening is inadequate for diagnostic testing, even though it is used widely.”

In order to further understand the distribution of CFTR mutations in the nonwhite groups, the scientists sequenced the DNA of interest in 140 individuals in the Registry. Results show that 89 patients had two CFTR variants, and 7 of these were novel. Furthermore, in the other 51 patients, 14 rearrangements were detected, six of which had not been previously described. These observations were obtained through Multiplex ligation-dependent probe amplification (MLPA), a method that researchers suggest would be a great addition to genetic testing.

The researchers also observed that more CF patients were being analyzed, with greater proportion of genetic profiling made between 2008 and 2013. In 2008, 21% of white patients were not yet genotyped compared to 9% in 2013. This trend was observed across the other ethnic groups as well. However, greater proportions of patients in these groups remained to be genotyped when compared to whites. In 2013, 19% of black patients remained to be genetically analyzed.

Later diagnosis translates into delayed treatment and worse prognosis. With this study, the researchers suggest that the information gathered can be used to optimize newborn screening programs, and therefore, increase equity between whites and nonwhites CF patients in early diagnosis and intervention.

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