The analysis only showed a mutation in one allele. CF is an autosomal recessive disease: the disease only manifests if there are mutations in both alleles of the CFTR gene.

If you still have 1 functional copy of the CFTR gene, you can still make the CFTR protein (the chloride channel/transporter), hence your body won’t have any issues.

This is analogous to tumor suppressor genes like Rb: so long as one of the alleles you have is functional, you can make enough of the protein to “make up” for the defective allele. If both get knocked out (Rb-/-), you lose the protection provided by the gene because now you make no protein at all.

The only thing that made sense for this question was the fact that the other allele was not included in the analysis.

ALLELIC HETEROGENEITY (FA page 57 2019)

Theres multiple allele variants for the CFTR gene in a single locus, so you could get cystic fibrosis from a mutation in any one of those allele variants(theres over 1500 different mutations described) the question stem mentioned they tested for the most common types, so we can assume they probably just missed testing for mutations in other alleles.

IRT is measured in routine heel-prick blood taken for biochemical screening of all newborn infants born in the UK. This test is one of a number of completed in newborn screening (the "Guthrie Test"). In Australia it is known 94% of those with eventual diagnosis of CF have a positive IRT on newborn screen. Samples with a raised IRT (defined as highest 1% of values) are then screened for common CF gene mutations. Each centre has a slightly different gene panel; currently 40-50 of the most common genes are sequenced. However, there are more than 2000 known mutations, so gene panel testing does miss occasional CF patients

If gene testing finds one mutation they will then have a sweat test to help confirm the diagnosis. Sweat testing is more likely to be equivocal in infants and typically not attempted in those under 5kg. If sweat test is positive more expansive gene testing is considered. If two mutations are found they are diagnosed with CF.

SIMPLE. 3 steps.

1. we know this girl has cystic fibrosis .

2. but testing shows only 1 allele is mutated.

3. since she has CF, the other allele CANNOT be normal , and the only explanation to her having CF is the panel didnt detect it.

you need a mutation in 2 alleles to get CF [since it is autosomal recessive]/

Another thing... Isn't it possible that both the sweat chloride test and the immunoreactive trypsin are just false +? Both of these tests have pretty low threshold for returning as a + response. Why can't it be possible that one allelic mutation is enough to cause a positive result in these tests, without actually signifying the pt has a disease? My only guess is that since two answers indicate that there could be a false positive, neither can be the right answer.