@28 See all the neat things I miss being a bacteriologist! Thanks a lot DM. Next proposal I submit will have a better introduction, that’s for sure.

It’s actually relatively well known – but of course completely irrelevant for the specific field of lung infection etiology / treatment studies – that milder CTFR alleles cause pancreatic issues almost inevitably, but lungs may remain healthy. There was a case study of twins one of whom developed pancreas and severe lung problems, while the other one has pancreatic problems but no Pseudomonas infection and no need for antibacterial regimen (as far as I recall they weren’t id twins, because the discussion dwelled on non-CTFR trans acting genetic factors)

“Leaky” splice mutations are especially fickle, with expression of full-length mRNA species varying from patient to patient and from tissue to tissue. In CTFR, partially penetrant splice mutations involve both canonic splice site consensi (for example poly-pyrimidine repeat length variants in the weak-ish splice acceptor of exon 9) and extraneous splice junctions (like a well-studied SNP which creates an alternative junction in the middle of an intron, many kb’s away from the exons; it results in a partial inclusion of a spurious exon, and therefore the functional mRNA level goes down). I think the rule of thumb is that until one loses 75% of “correct” mRNA species in the lung epithelium, the lungs stay healthy; and only after 90%+ mRNA is lost, then the lung disease becomes inevitable.

The medical basis for the concern is that transmission of infections between CF patients is a real thing and results in segregation of Burkholderia cepacia complex (primarily B. cenocepacia and B. multivorans, but there are others) positive and negative individuals. Colonization with Bcc organisms frequently, but not always, marks the worsening of conditions and can lead to rapid death. Bcc infections are a relative recent phenomenon. In the 1970s CF patients didn’t get them, in part because they died from their P. aeruginosa infections earlier in life. While P. aeruginosa infections of CF patients are not typically spread patient to patient (although epidemic strains are turning up now), Bcc infections are spread from patient to patient. (There’s a lot of evolution/microbiology to explain this, I’ll spare you all )

With that in mind, if a school does not feel they can appropriately segregate students with CF they run the risk of infection transmission. This appears to be the case for this school.

HOWEVER, the various stories I’ve read about this have not made clear what the new student’s genetic condition is. The parents have said that various tests have indicated that he has normal lung function, which I would think simplifies the issue because people with normal lung function don’t get Bcc (or P. aeruginosa) lung colonization.

Until this morning, I was completely unaware that there were CF alleles that someone can be homozygous for, or heterozygous with 2 different mutant alleles, that result in some CF symptoms but normal lung function. I say this as a researcher of CF pathogenic bacteria, so it’s not the most common knowledge and I can easily see the school district not knowing this.

So the student either has some set of CF alleles that leave him with normal lung function, or he’s heterozygous carrier like ~5% of the European descended population. If he’s simply a carrier I cannot imagine his parents filling out a health form and noting that fact, but its possible I suppose.

Either way, if he has normal lung function then I don’t see a need for segregation. Presumably to be safe they’d want to verify periodically that there hasn’t been an onset of lung dysfunction, but I assume that is part of medical treatment for someone with CF in the first place.

But another tidbit worth noting is the headline of the piece, about Terminally Ill Children. CF is essentially written off as an incurable terminal childhood disease there, and virtually no CF chidren survive into even early adulthood (Late Katia Kostromina, a local CF community organizer hero, had a rare distinction of living till 20)

nowhere have I been able to find a reference to exactly what and how many mutations he has. I did find one that notes his parents have not released that information. http://theweek.com/article/index/235143/the-boy-kicked-out-of-school-for-carrying-a-cystic-fibrosis-gene

the SF Chronicle story says, “In the evolving field of cystic fibrosis diagnosis and treatment, there is debate about which variations mean someone has the disease versus being a carrier only.
Because of Colman’s rare genetic combination, his parents and doctors have closely monitored him to make sure he doesn’t have the disease.
His physician has documented that he doesn’t, and he never had a clinical diagnosis of the disease, his parents said.”

why would they continue monitoring if he only has one copy? why would the parents not be trumpeting, “heterozygous, no problem” ?

Just for reference, the CF carrier rate is 1 in 25 to 30 people. That means there are millions of carriers walking around and we certainly don’t hear of this frightening increased risk of infection impacting literally millions of Americans each year. It seems that the relative risk is being significantly exaggerated. If such a risk truly threatened affected individuals, wouldn’t it be especially unsafe for them to live in homes with two CF carriers, i.e. their parents, where they are sharing food, facilities and air?

From the article: “A few weeks into the school year at Jordan Middle School, school officials took note of Colman’s medical history, information that eventually was shared with another Jordan parent whose two children have classic cystic fibrosis and are predisposed to chronic lung infections.”

Another interesting twist is that the school may have claimed that they are transfering this child to protect him rather than those other students with CF, citing a 2003 paper which claimed that asymptomatic CF carriers are also at risk for picking the bacterial infection from CF patients?

But then, as some readers comment, if a school must protect asymptomatics, then it should administer a compulsory genetic test to all students attending the same school as a CF patient!

Others claim that the school must have violated HIPAA, but it sounds far fetched. It appears that the public disclosure came from the parents, as they geared to fight the school transfer, rather than from the school itself?

Being a carrier of the CF allele (one copy), give the carrier some degree of genetic protection from cholera. So you find higher incidences where the historically, endemic cholera rates were high; ie Ireland.

genes are different (because you can’t change them with current tech). but parents make minors do all sorts of crazy shit.

If GINA applied, then it would have been illegal to discriminate on the basis of genetic makeup, but this isn’t a workplace.

What I also find fascinating is that the parents chose to disclose genetic info of their child, apparently w/o any overriding reason to do so. And they have guts to call their line of reasoning “an overabundance of caution“! Some caution, yeah right …. You really gotta be more careful with disclosure of the genetic makeup of the minors who can’t consent!

In total about 1 in 19 of the population (5.26%) of population are carriers of relevant alleles. Looking at some stats I see the prevalance of CF in newborns in Ireland is: 1 in every 1,461 live births. By comparison the overall European average is 1 in every 3,500 live births.

Northern Ireland = 1 in every 1,850 live births
England = 1 in every 2,500 live births

-Paul

If this kid has B. cepacia, he is not unsymptomatic.