In the news

Review data from 2002-09 on the cystic fibrosis (CF) carrier and diagnostic testing offered by Quest Diagnostics in California, in order to evaluate the performance of a panel of 23 mutations recommended by the American College of Medical Genetics (ACMG) and American College of Obstetricians and Gynaecologists (ACOG).

Using a databases containing over 3 million CF screening tests with a mutation panel of 23-32 mutations, and nearly 4000 sequencing analyses of the CFTR gene, the authors observed a carrier rate of 1:34 with a detection rate of 85% (and almost 100% in Caucasians) based on the estimated US pan-ethnic carrier rate of 1:29. 

Limiting the carrier mutations detected to just the ACMG/ACOG core panel would have reduced the detection rate by only 1%. The authors estimate that around 1 in 1149 couples would be identified as at risk for conceiving a child with CF using this panel, of whom around two-thirds would opt for prenatal diagnostic testing. Of 62 newborns with CF, the majority (64%) were compound heterozygotes of one panel mutation and a mutation not on any panel.

There is no evidence that including additional rarer mutations in the panel would substantially improve the carrier detection rate. Furthermore, because 27% of individuals diagnosed with atypical or mild CF in this study had only a single CFTR mutation, no current molecular method alone is capable of detecting all newborns with CF.

This large study indicates that CF carrier testing based on a limited number of the most common mutations performs well even in an ethnically diverse population. The finding has implications not only for the design of national screening programmes but also for the various commercial companies offering CF carrier testing based on many more mutations, including the leading consumer genomics company 23andMe which has recently substantially expanded its genotyping platform (see Genetic Future).