<div class="FTQUOTE"><begin quote>There is a hierarchy of tissue manifestations based on the amount of functioning CFTR expressed on the epithelial cell surface.2 As knowledge of the genetic defect in CF increases, it appears that complex CFTR genotypes and other genes are capable of modifying the CF phenotype. One such example occurs in intron 8 of the CFTR gene in which a variable number of thymidines influences the amount of normal CFTR mRNA produced.3 The more thymidines present, the more normally spliced CFTR mRNA produced. However, if the remainder of the CFTR molecule is normal, these splice variants are usually of little clinical significance. If a CFTR mutation exists that further reduces function, the splice variant may be more critical.4 For example, the mutation R117H appears to have arisen twice, once on a 5 thymidines (5T) background and once on a 7 thymidines (7T) background, whereas, F508 appears to have arisen on the 9 thymidines (9T) background. The R117H mutation has significant residual activity, and males with this mutation and a 7T splice variant in combination with a second mutant CFTR allele may only have congenital bilateral absence of the vas deferens.5,6 Many of these patients are otherwise well and do not have elevated sweat chloride concentrations or lung disease typical of CF.6 When the R117H mutation occurs on the 5T background and in combination with more severe CF mutations, it usually results in a pancreatic sufficient form of CF.6 The 5T allele is a mutation with partial penetrance and when associated with a second mutation in CFTR on the other chromosome, may result in variable disease presentations.4 Because of the potential complications of incorrect conclusions being made solely based on simple genotype analysis, the National Institutes of Health panel reconvened and rescinded its initial recommendation. </end quote></div>I am sorry to hear about your granson & welcome!!! My 5 year old with CF is R117H-5T & she is NOT classified as a-typical. She wasn't dx until she was 4 but has not digestional involvement. I do believe from prior research that 5T is more severe than the 7T allele. I found this on the internet a while back
