Carrier screening for cystic fibrosis in the new era of medications that restore CFTR function

摘要

Carrier screening for cystic fibrosis involves analysis for common mutations in the CFTR gene from people with no personal history, or family history, of the disease. This analysis shows whether a person is a carrier, at risk (one in four) of having a baby with cystic fibrosis if their partner is also a carrier. Carrier screening has been recommended by the American College of Medical Genetics and American College of Obstetricians and Gynecologists (ACMG/ACOG),1 and the Human Genetics Society of Australasia (HGSA),2 and has been established in the USA, Australia, and parts of Europe.3 Carrier screening has been shown to reduce the proportion of livebirths with cystic fibrosis by 50% in two US states, 50% in Edinburgh, and 75% in northeastern Italy.4, 5, 6, 7 In these series, most of the remaining cystic fibrosis births have resulted from couples choosing to continue affected pregnancies to term, rather than from affected fetuses missed by screening. The widespread introduction of carrier screening for cystic fibrosis has been limited by several issues for health-care providers and policy makers, including variable phenotype of patients with the same genotype, the numerous mutations associated with cystic fibrosis, low public awareness of the disease, infrastructure for preconception and prenatal care, genetic counselling resources, and health economic considerations.3, 8 Resolution of these issues has been slow. Furthermore, a new issue has emerged—namely, the development of CFTR restorative therapy that challenges the idea that cystic fibrosis is not curable. We discuss the implications of CFTR restorative therapy on carrier screening for cystic fibrosis.