title: Phenotypes of California CF Newborn Screen-Positive Children with CFTR 5T Allele by TG Repeat Length.
abstract: BACKGROUND
  At the cystic fibrosis transmembrane conductance regulator (CFTR) gene (IVS8)-(TG)m(T)n locus, a lower number of thymidines (legacy names 9T vs. 7T vs. 5T) and a higher number of (TG) repeats (TG-11 vs. 12 vs. 13) are associated with decreasing translation of functional CFTR protein in vitro.
  
  
  METHODS
  Retrospective cohort study comparing phenotypes of California CF newborn screen-positive children (followed 2-8 years) who had two CF-causing mutations (diagnosed as CF) with those who had one mutation from a panel of 40 CF-causing mutations (CF40mut) and one (IVS8)-(TG)11, 12, or 13-5T mutation detected by sequencing (diagnosed as CFTR-related metabolic syndrome [cRMS]).
  
  
  RESULTS
  The study included 428 children, of which 234 had two CF-causing mutations, and were used to compare with the other 194 children with one CF-causing mutation and one isolated 5T allele [CF40mut/(TG)13-5T = 21, CF40mut/(TG)12-5T = 85, and CF40mut/(TG)11-5T = 88]. Among children with CF40mut/(TG)13-5T, 38% were diagnosed with CF by 8 years, based on sweat chloride results and clinical presentation. Six percent of those with CF40mut/(TG)12-5T, and none with CF40mut/(TG)11-5T, reached diagnostic criteria.
  
  
  CONCLUSIONS
  CFTR (IVS8)-(TG)m-5T allele (TG) tract length determination provides valuable information in predicting the risk of developing a CF phenotype. Of the three types of 5T alleles evaluated, screen-positive children with genotype CF40mut/(TG)13-5T progressed from CRMS to CF at a high rate, while there was little evidence of clinical disease in those with CF40mut/(TG)11-5T. Additional data from longer follow-up intervals are needed to fully understand the natural history of individuals with a CF40mut/(TG)m-5T genotype.
authors.affiliation: 1 Department of Pediatric Pulmonology, Keck School of Medicine, Children's Hospital Los Angeles, University of Southern California , Los Angeles, California.
authors.forename: Danieli Barino
authors.initials: DB
authors.lastname: Salinas
authors.affiliation: 2 Department of Biostatics, Southern California Clinical and Translational Science Institute, Children's Hospital Los Angeles, University of Southern California , Los Angeles, California.
authors.forename: Colleen
authors.initials: C
authors.lastname: Azen
authors.affiliation: 3 Sequoia Foundation , La Jolla, California.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Young
authors.affiliation: 1 Department of Pediatric Pulmonology, Keck School of Medicine, Children's Hospital Los Angeles, University of Southern California , Los Angeles, California.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Keens
authors.affiliation: 4 Environmental Health Investigations Branch , California Department of Public Health, Richmond, California.
authors.forename: Martin
authors.initials: M
authors.lastname: Kharrazi
authors.affiliation: 5 Department of Pediatric Newborn Medicine, Brigham and Women's Hospital , Harvard Medical School, Boston, Massachusetts.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Parad
mesh_terms: D000483:Alleles; D002140:California; D002675:Child, Preschool; D015331:Cohort Studies; D003550:Cystic Fibrosis / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics* / Q000378:metabolism; D018900:Dinucleotide Repeats; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D010641:Phenotype; D012189:Retrospective Studies
chemical_list: C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator