Novel CFTR variants identified during the first 3 years of cystic fibrosis newborn screening in California

Lisa Prach, Ruth Koepke, Martin Kharrazi, Steven Keiles, Danieli B. Salinas, Maria Carmen Reyes, Mark Pian, Harry Opsimos, Kimberly N. Otsuka, Karen Ann Hardy, Carlos E. Milla, Jacquelyn M. Zirbes, Bradley Chipps, Susan O'Bra, Muhammad M. Saeed, Reddivalam Sudhakar, Susan Lehto, Dennis Nielson, Gregory F. Shay, Mary SeastrandSanjay Jhawar, Bruce Nickerson, Christopher Landon, Ann Thompson, Eliezer Nussbaum, Terry Chin, Henry Wojtczak

Research output: Contribution to journalArticle

24 Scopus citations


California uses a unique method to screen newborns for cystic fibrosis (CF) that includes gene scanning and DNA sequencing after only one California-40 cystic fibrosis transmembrane conductance regulator (CFTR) panel mutation has been identified in hypertrypsinogenemic specimens. Newborns found by sequencing to have one or more additional mutations or variants (including novel variants) in the CFTR gene are systematically followed, allowing for prospective assessment of the pathogenic potential of these variants. During the first 3 years of screening, 55 novel variants were identified. Six of these novel variants were discovered in five screen-negative participants and three were identified in multiple unrelated participants. Ten novel variants (c.2554-2555insT, p.F1107L, c.-152G>C, p.L323P, p.L32M, c.2883-2886dupGTCA, c.2349-2350insT, p.K114del, c.-602A>T, and c.2822delT) were associated with a CF phenotype (42% of participants were diagnosed at 4 to 25 months of age), whereas 26 were associated with CFTR-related metabolic syndrome to date. Associations with the remaining novel variants were confounded by the presence of other diseases or other mutations in cis or by inadequate follow-up. These findings have implications for how CF newborn screening and follow-up is conducted and will help guide which genotypes should, and which should not, be considered screen positive for CF in California and elsewhere.

Original languageEnglish (US)
Pages (from-to)710-722
Number of pages13
JournalJournal of Molecular Diagnostics
Issue number5
StatePublished - Sep 2013

ASJC Scopus subject areas

  • Molecular Medicine
  • Pathology and Forensic Medicine

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    Prach, L., Koepke, R., Kharrazi, M., Keiles, S., Salinas, D. B., Reyes, M. C., Pian, M., Opsimos, H., Otsuka, K. N., Hardy, K. A., Milla, C. E., Zirbes, J. M., Chipps, B., O'Bra, S., Saeed, M. M., Sudhakar, R., Lehto, S., Nielson, D., Shay, G. F., ... Wojtczak, H. (2013). Novel CFTR variants identified during the first 3 years of cystic fibrosis newborn screening in California. Journal of Molecular Diagnostics, 15(5), 710-722.