PEDIATRICS Vol. 119 No. 3 March 2007, pp. 647a-648 (doi:10.1542/peds.2006-3532)
LETTER TO THE EDITOR |
Pulmonary Manifestations in 
F508/R117H: In Reply
Brian P. O'Sullivan, MD
Department of Pediatrics
University of Massachusetts Medical School
Worcester, MA 01655
Anne Marie Comeau, PhD
New England Newborn Screening Program and Department of Pediatrics
University of Massachusetts Medical School
Jamaica Plain, MA 02130
Richard Parad, MD
Department of Newborn Medicine
Brigham and Women's Hospital and Children's Hospital
Boston, MA 02115
We appreciate Dr Ren's comments regarding our report of 4 children with the genotype 
F508/R117H-7T.1 He reports the case of another child identified by a positive immunoreactive trypsinogen/DNA cystic fibrosis (CF) newborn screen with a F508/R117H-7T genotype who grew Pseudomonas aeruginosa from an oropharyngeal culture and demonstrated airway obstruction on infant pulmonary-function testing. We believe these 5 cases, along with those reported by Lording et al,2 supply ample evidence that the F508/R117H-7T genotype is not necessarily benign. This experience contrasts with the conclusions of the report by Scotet et al3 in the November issue of Pediatrics. They reported a series of infants with elevated immunoreactive trypsinogen and the F508/R117H-7T genotype and concluded that there was significantly better pulmonary function in the R117H compound heterozygotes as compared with age-matched controls with 2 severe CF mutations. Unfortunately, FEV1 (forced expiratory volume in 1 second) data were only available for 2 of 9 R117H compound heterozygotes. Also, although only 1 of 9 R117H compound heterozygotes versus 5 of 9 controls grew P aeruginosa from respiratory cultures, the authors did not state how many of the R117H compound heterozygotes had sputum or oropharyngeal cultures obtained or how frequently they were obtained.
Scotet et al3 recommend removal of R117H from the CF newborn screening mutation panel on the basis of this very limited data set. Our findings,1 as well as those of Ren and Lording et al,2 demonstrate that children with this mutation are at some risk of Pseudomonas colonization and infection, respiratory symptoms, and abnormal pulmonary-function test results. We believe it is premature to recommend removal of R117H from CF newborn screening mutation panels. Larger longitudinal studies need to be performed. We continue to recommend that all infants identified with R117H-7T as 1 of 2 CF transmembrane conductance regulator (CFTR) mutations be followed by a CF clinician, including evaluation for CF flora, chest imaging, and pulmonary-function testing, when it can be performed.
REFERENCES
- O'Sullivan BP, Zwerdling RG, Dorkin HL, Comeau AM, Parad R. Early pulmonary manifestation of cystic fibrosis in children with the DeltaF508/R117H–7T genotype.
Pediatrics. 2006;118
:1260
–1265
[Abstract/Free Full Text] - Lording A, McGaw M, Dalton A, Beal G, Everard M, Taylor CJ. Pulmonary infection in mild variant cystic fibrosis: implications for care. J Cyst Fibros. 2006;5 :101 –104[CrossRef][Medline]
- Scotet V, Audrezet MP, Roussey M, et al. Immunoreactive trypsin/DNA newborn screening for cystic fibrosis: should the R117H variant be included in CFTR mutation panels? Pediatrics. 2006;118(5) . Available at: www.pediatrics.org/cgi/content/full/118/5/e1523
PEDIATRICS (ISSN 1098-4275). ©2007 by the American Academy of Pediatrics
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