A research team from the University of Helsinki have identified a new genetic mutation that alters the function of cryopyrin and leads to a life-long periodic inflammation of the cornea , the transparent window of the human eye . The study was published in the  American Journal of Ophthalmology

Dr. Valle named the disease keratitis fugax hereditary  and it was found that the inflammation primarily affected the corneal endothelium, a cell layer that covers the back of the cornea, an observation that identified the disease as a keratoendotheliitis.

Dr. Turunen recruited thirty patients from seven families and four patients who appeared to have the disease but could not name any affected relative.

After first sequencing the protein coding regions of all chromosomes from ten patients, I found that there was an identical point mutation in the Nucleotide-Binding Domain, Leucine-Rich Repeat Family, Pyrin Domain-Containing 3 ( NLRP3 ) gene that codes cryopyrin.

"Cryopyrin mutations were known to cause rare periodic autoinflammatory syndromes , diseases in which the white blood cells of the human body become activated without any stimulus," said Kivelä.

The team subsequently confirmed by direct sequencing that the same mutation was present in all other affected family members and absent from those that had healthy eyes.

Keratoendotheliitis fugax hereditaria is the fourth cryopyrin-associated periodic syndrome. The other three – familial cold autoinflammatory syndrome, Muckle-Wells syndrome, and chronic infantile neurological, cutaneous, articular syndrome affect multiple organs and can be debiliating.

Like keratoendotheliitis fugax hereditary, they emerge during childhood, but their hallmarks are episodic fevers, skin rashes, and inflammation of the joints, gastrointestinal tract and the nervous system rather than ocular irritation.

"Intriguingly, although a few minor finding in these syndromes, the patients nevertheless have been reported to show ocular inflammatory signs and some have developed similar corneal opacities than what we see in our patients with hereditary keratoendotheliitis fugax," said Turunen.

"We believe that the mutation that underlies keratoendotheliitis fugax either is a milder form of the spectrum in which only the eye is sensitive enough to become symptomatic, or faulty activation of cryopyrin is entirely restricted to the eye".

"Now that the gene has been identified, we have reason to believe that the disease is actually more universal. Exome databases show that carriers of this mutation exist in other populations with European ancestry as well, with a comparable frequency to that in Finns", said Anna-Elina Lehesjoki.

"The carrier frequency in the ExAC database suggests that up to one in 20,000 Caucasians may be predisposed to develop symptoms of keratoendotheliitis."

"We expect that patients to emerge more widely that the diagnosis could be made by genetic testing . We were just the lucky ones to be informed early of the existence of this intriguing corneal disease, thanks to the astute observations by Dr. Valle".

At the moment, no specific treatment for keratoendotheliitis fugax hereditaria is known. The other cryopyrin-associated periodic syndromes have responded to drugs that target interleukin-1-beta , downstream mediator of the cryopyrin cascade