Both authors contributed equally to this work.
Cystic fibrosis mutations for p.F508del compound heterozygotes predict sweat chloride levels and pancreatic sufficiency
Version of Record online: 29 NOV 2011
© 2011 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd
Volume 82, Issue 6, pages 546–551, December 2012
How to Cite
Sebro, R., Levy, H., Schneck, K., Dimmock, D., Raby, B., Cannon, C., Broeckel, U. and Risch, N. (2012), Cystic fibrosis mutations for p.F508del compound heterozygotes predict sweat chloride levels and pancreatic sufficiency. Clinical Genetics, 82: 546–551. doi: 10.1111/j.1399-0004.2011.01804.x
- Issue online: 6 NOV 2012
- Version of Record online: 29 NOV 2011
- Accepted manuscript online: 28 OCT 2011 03:19PM EST
- Received 3 September 2011, revised and accepted for publication 25 October 2011
- cystic fibrosis;
- pulmonary function;
- sweat chloride
Sebro R, Levy H, Schneck K, Dimmock D, Raby BA, Cannon CL, Broeckel U, Risch NJ. Cystic fibrosis mutations for p.F508del compound heterozygotes predict sweat chloride levels and pancreatic sufficiency.
Cystic fibrosis (CF) is a monogenetic disease with a complex phenotype. Over 1500 mutations in the CFTR gene have been identified; however, the p.F508del mutation is most common. There has been limited correlation between the CFTR mutation genotype and the disease phenotypes. We evaluated the non-p.F508del mutation of 108 p.F508del compound heterozygotes using the biological classification method, Grantham and Sorting Intolerant from Tolerant (SIFT) scores to assess whether these scoring systems correlated with sweat chloride levels, pancreatic sufficiency, predicted FEV1, and risk of infection with Pseudomonas aeruginosa in the last year. Mutations predicted to be ‘mild’ by the biological classification method are associated with more normal sweat chloride levels (p < 0.001), pancreatic sufficiency (p < 0.001) and decreased risk of infection with Pseudomonas in the last year (p = 0.014). Lower Grantham scores are associated with more normal sweat chloride levels (p < 0.001), and pancreatic sufficiency (p = 0.014). Higher SIFT scores are associated with more normal sweat chloride levels (p < 0.001) and pancreatic sufficiency (p = 0.011). There was no association between pulmonary function measured by predicted FEV1 and the biological classification (p = 0.98), Grantham (p = 0.28) or SIFT scores (p = 0.62), which suggests the pulmonary disease related to CF may involve other modifier genes and environmental factors.