The new face of cystic fibrosis in the era of population genetic carrier screening

Miri Dotan, Hannah Blau, Amihood Singer, Patrick Stafler, Dario Prais, Malena Cohen-Cymberknoh, Joel Reiter, Ori Efrati, Adi Dagan, Lea Bentur, Michal Gur, Galit Livnat, Karin Yaacoby-Bianu, Micha Aviram, Inbal Golan Tripto, Ophir Bar-On, Reut Matar, Shani Hagit, Mira Malcov, Gheona AltarescuHanna Segev, Baruch Feldman, Eitan Kerem, Meir Mei-Zahav*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Population genetic carrier screening (PGCS) for cystic fibrosis (CF) has been offered to couples in Israel since 1999 and was included in a fully subsidized national program in 2008. We evaluated the impact of PGCS on CF incidence, genetic and clinical features. Methods: This was a retrospective national study. Demographic and clinical characteristics of children with CF born in Israel between 2008 and 2018 were obtained from the national CF registry and from patients' medical records. Data on CF births, preimplantation genetic testing (PGT), pregnancy termination and de-identified data from the PGCS program were collected. Results: CF births per 100,000 live births decreased from 8.29 in 2008 to 0.54 in 2018 (IRR = 0.84, p < 0.001). The CF pregnancy termination rate did not change (IRR = 1, p= 0.9) while the CF-related PGT rate increased markedly (IRR = 1.33, p < 0.001). One hundred and two children were born with CF between 2008 and 2018 with a median age at diagnosis of 4.8 months, range 0–111 months. Unlike the generally high uptake nationally, 65/102 had not performed PGCS. Even if all had utilized PGCS, only 51 would have been detected by the existing genetic screening panel. Clinically, 34 % of children were pancreatic sufficient compared to 23 % before 2008 (p = 0.04). Conclusions: Since institution of a nationwide PGCS program, the birth of children with CF decreased markedly. Residual function variants and pancreatic sufficiency were more common. A broader genetic screening panel and increased PGCS utilization may further decrease the birth of children with CF.

Original languageEnglish
JournalJournal of Cystic Fibrosis
DOIs
StateAccepted/In press - 2023

Keywords

  • Antenatal screening
  • Cystic fibrosis
  • Population carrier screening
  • Pre-implantation genetic diagnosis

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