Cystic fibrosis population carrier screening: Here at last—Are we ready?

Updated assessment of cystic fibrosis mutation frequencies in non-Hispanic Caucasians

“…As a partial solution, reflexive testing has been recommended to identify those in whom the mutation could cause cystic fibrosis in the offspring in combination with a second disease-causing mutation. 4,5 A second mutation (I148T) in the expanded panel is also being reported more frequently in the general population, again indicating low penetrance. 13,14 These findings indicate that the composition of the panel may benefit from being revised.…”

“…3 Recently, the American College of Medical Genetics (ACMG) published laboratory standards and guidelines for prenatal cystic fibrosis screening, including a recommended core testing panel of 25 mutations. 4,5 When estimating the proportion of carrier couples (or affected fetuses) who can be identified by such a panel, it is first necessary to derive mutation frequencies from a large, unbiased sampling of individuals with clinically defined cystic fibrosis whose race/ethnicity are known. The ACMG laboratory guidelines provide an estimated cumulative frequency of 80% for Caucasians of European heritage but do not include individual estimates of mutation frequencies.…”

Genetics in medical practice

“…The scope of carrier testing for couples contemplating pregnancy is increasing, exemplified by the introduction of cystic fibrosis carrier screening. 6 This will increase the need for a medical genetics workforce, especially genetic counselors. Tandem mass spectrometry is increasing the scope of newborn screening, which may place additional demands on clinical services for inborn errors of metabolism.…”

The Cystic Fibrosis mutation “arms race”: when less is more

“…2,3 Details of exactly how such a program should be implemented were considered at a second consensus conference held in 1998 4 and then worked out by a steering committee comprised of representatives from ACMG, ACOG, and NHGRI. 5 Subcommittees were formed to work out the three essential prongs of the effort: (1) patient education and informed consent; (2) laboratory testing (including the minimum core panel of mutations to be screened), interpretation, and reporting; and (3) provider education. As is now well known, the second of these subcommittees recommended a universal (pan-ethnic) screening panel of 25 CFTR mutations, which met the dual criteria of known association with CF and having an allele frequency in the affected US population of Ն0.1%, based on data maintained by the Cystic Fibrosis Foundation and others.…”