Frequency of intron 8 CFTR polythymidine sequence variant in neonatal blood specimens

The relationship between neonatal immunoreactive trypsinogen, Delta F508, and IVS8-5T

“…5 The intron 8 polythymidine sequence regulates the splicing of exon 9 in transcription of the cystic fibrosis transmembrane conductance regulator protein (CFTR) 6. IVS8-5T is associated with the least efficient splicing of CFTR, but whether the frequency of IVS8-5T increases with increasing level of IRT, in the absence of another mutation, is unknown.…”

Impact of IVS8-(TG)m(T)n on IRT and sweat chloride levels in newborns identified by California CF newborn screening

“…Previous studies relating IRT to (T) length have found a higher prevalence of the 5T allele among newborns with elevated neonatal IRT [9,12]. In a large Massachusetts CFNBS cohort, a 3-fold increase in 5T allele frequency was seen in infants with IRT above the 90th percentile relative to below it [13].…”

“…Few have investigated the relation of these haplotypes with CF diagnostic (sweat chloride (SC)) [9,10] and newborn screening (CFNBS) (immunoreactive trypsinogen (IRT)) [9,[11][12][13][14] tests. We sought to determine the relation of number of (TG) repeats at the (TG)m(T)5 locus of CFNBS-identified hypertrypsinogenemic (HT) infants with genotype ΔF508-9T/5T (ΔF508 in trans with only a 5T allele and no other CFTR mutation) with IRT and SC.…”

Cancer Genetics and Insurance

“…However, the carrier frequency among nonaffected IRT-positive babies is almost three times higher than that in the general population (Laroche et al 1991;Castellani et al 1997); this could be partially explained if some of these babies carry on the other chromosome a mild mutation, associated with scarce symptoms and normal sweat chloride values. A DNA polymorphic sequence of five thymines (TTTTT) in intron 8 of the CF transmembrane conductance regulator (CFTR) gene, which is very common in men with a primarily genital CF form called "congenital bilateral absence of the vas deferens" (CBAVD) (Chillon et al 1995), has been found to occur more frequently in newborns with raised IRT values than in controls (Castellani et al 1997;Chin et al 1997). To look further into the hypothesis that, in at least some babies, raised trypsin levels at birth could be a phenotypic expression of a compound heterozygosity, we investigated a subset of 18 newborns, using the following selection criteria: IRT 199.5 percentile; one identified CFTR mutation among a panel of 15 mutations that are present in 85% of the CF chromosomes in our area; normal sweat chloride, as determined by pilocarpine iontophoresis (mean 16.9 mEq/liter; maximum 32 mEq/liter; minimum 6 mEq/liter).…”