Benign outcome among positive cystic fibrosis newborn screen children with non-CF-causing variants

Danieli Barino Salinas; Patrick R Sosnay; Colleen Azen; Suzanne Young; Karen S Raraigh; Thomas G Keens; Martin Kharrazi

doi:10.1016/j.jcf.2015.03.006

Benign outcome among positive cystic fibrosis newborn screen children with non-CF-causing variants

J Cyst Fibros. 2015 Nov;14(6):714-9. doi: 10.1016/j.jcf.2015.03.006. Epub 2015 Mar 29.

Authors

Danieli Barino Salinas¹, Patrick R Sosnay², Colleen Azen³, Suzanne Young⁴, Karen S Raraigh⁵, Thomas G Keens⁶, Martin Kharrazi⁷

Affiliations

¹ Pediatrics-Pediatric Pulmonology, Keck School of Medicine, Children's Hospital Los Angeles, University of Southern California (USC), 4650 Sunset Boulevard, MS 83, Los Angeles, CA 90027, USA. Electronic address: [email protected].
² McKusick-Nathans Institute of Medical Genetics, Medicine-Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, 5th Floor, 1830 E. Monument St., Baltimore, MD 21287, USA. Electronic address: [email protected].
³ Southern California Clinical and Translational Science Institute, Children's Hospital Los Angeles, University of Southern California, 4650 Sunset Boulevard, MS 142, Los Angeles, CA 90027, USA. Electronic address: [email protected].
⁴ The Sequoia Foundation, 2166 Avenida De La Playa, La Jolla, CA 92037, USA. Electronic address: [email protected].
⁵ McKusick-Nathans Institute of Medical Genetics, Johns Hopkins University, Johns Hopkins University School of Medicine, 733 North Broadway, MRB 553, Baltimore, MD 21287, USA. Electronic address: [email protected].
⁶ Pediatrics-Pediatric Pulmonology, Keck School of Medicine, Children's Hospital Los Angeles, University of Southern California (USC), 4650 Sunset Boulevard, MS 83, Los Angeles, CA 90027, USA. Electronic address: [email protected].
⁷ Environmental Health Investigations Branch, California Department of Public Health, 850 Marina Bay Parkway, P-3, Richmond, CA 94804, USA. Electronic address: [email protected].

Abstract

Background: The Clinical and Functional Translation of CFTR project (CFTR2) classified some cystic fibrosis transmembrane conductance regulator (CFTR) gene variants as non-cystic fibrosis (CF)-causing. To evaluate this, the clinical status of children carrying these mutations was examined.

Methods: We analyzed CF disease-defining variables over 2-6 years in two groups of California CF screen- positive neonates born from 2007 to 2011: (1) children with two CF-causing variants and (2) children with one CF-causing and one non-CF-causing variant, as defined by CFTR2.

Results: Children carrying non-CF-causing variants had significantly higher birth weight, lower immunoreactive trypsinogen and sweat chloride values, higher first year growth curves, and a lower rate of persistent Pseudomonas aeruginosa colonization compared to children with two CF-causing variants.

Conclusions: The outcomes in children 2-6 years of age with the L997F, G576A, R1162L, V754M, R668C, R31C, and S1235R variants are consistent with the CFTR2 non-CF-causing classification.

Keywords: CF-causing variants; CFTR2; Cystic fibrosis; Genotype-phenotype associations; Newborn screening; Non-CF-causing variants.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Cohort Studies
Cystic Fibrosis / diagnosis
Cystic Fibrosis / genetics*
Cystic Fibrosis Transmembrane Conductance Regulator / genetics*
Female
Humans
Infant, Newborn
Male
Mutation*
Neonatal Screening*
Retrospective Studies

Substances

Cystic Fibrosis Transmembrane Conductance Regulator

Abstract

Publication types

MeSH terms

Substances

Grants and funding