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an excess of warts

Like many young women her age, my daughter recently received information about Gardasil, a vaccine that offers protection against some types of the human papilloma virus (HPV). HPV is a virus that infects the skin & mucous membranes. It comes in more than 100 forms, some of which cause things like warts (including genital warts). Others are implicated in various cancers, including cervical cancer (which is where Gardasil comes in).

Warts on the skin, particular on hands & feet, are fairly common. Most of us aren't bothered by them (although 'plantar warts' - those on the soles of your feet - can make walking painful. I know, having had them!), because our immune systems keep them pretty much under control. But in rare individuals the immune system can't manage to destroy the virus-infected cells, & this can lead to some bizarre & unfortunate outcomes.

What sparked these musings? A report on the 'tree man of Indonesia', a man called Dede Kosawa who has such extreme warty overgrowths on hands & feet that he can neither walk properly nor use his hands.

Doctors believe Dede Kosawa's unusual appearance occurred because of a immune defect and HPV.

Dede first came to the world's attention in late 2007, when doctors began a series of operations that were to remove more than 6 kilograms of warty hummocks & tendrils from his extremities. When he returned home in August last year, the doctors hoped that a combination of the surgery & high-dose vitamin A would see him able to lead a fairly normal life. Unfortunately this hasn't happened, & they now say Dede will need twice-yearly operations for the rest of his life to keep the growths under control.

The technical name for Dede's symptoms is epidermodysplasia verruciformis, which appears to be due to an autosomal recessive mutation. Two genes on human chromosome 17, called the EVER1 & EVER2 genes, appear to be implicated in the cell's transport & use of zinc. Zinc is a cofactor for some viral proteins, & seems that these 2 genes are involved in blocking viral access to the cell's zinc. So mutations that inactivate one or both of these genes may leave the body open to epidermodysplasia verriuciformis, because the virus is able to use cellular zinc stores & grow beyond the immune system's ability to control it. Thankfully, the mutation is rare - but this is cold comfort to those few individuals who inherit two mutated EVER alleles and consequently suffer from this disfiguring disease.

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2 Comments

Thanks for posting this. I saw an article about this guy a few days ago, but let it pass.

What got me interested was your mention of zinc regulation/transport. (The connection with skin cancer is interesting too.) Zinc is also bound by a wide range of proteins, including many gene regulatory proteins, among them the so-called 'zinc finger' proteins. I've never given a lot of thought as to how zinc finger proteins acquire their zinc, mostly because it's "upstream" of my own interest in these proteins. All the same it seemed a silly thing to not know, as without their zinc they'd be non-functional (and probably degraded). There doesn't seem to be any reports linking this disease or the EVER-1 and EVER-2 proteins with zinc finger proteins (yet). Sometimes these odd links do actually lead somewhere, but no dice on this one it seems! I've taken a note of it in case a connection appears later. Who knows?!

I ran into another rather sad trio of cases reported in PMID: 17457453,

We described 3 male patients with epidermodysplasia verruciformis seen in the Department of Dermatology and Venereology, Baghdad Teaching Hospital; their ages were 25, 30 and 34 years subsequently. They developed frequent multiple basal and squamous cell carcinoma, all of them had periorbital squamous cell carcinoma that invaded the orbit and ended with enucleation of their eyes. All available therapeutic measures failed to inhibit the progressiveness of these tumors. Great awareness and early management must be performed regarding any periorbital lesion in epidermodysplasia verruciformis patients.

By 'enucleation of their eyes', I would think that they mean removal of the patients' eyes.

This from Iraq, so whatever state their country is in, they're doing medical research, which is good to see.

I first heard about it last year, when Dede was going home from hospital & everyone's hopes seemed to be high that the surgery + vit.A would do the trick. I guess that without dealing with the underlying genetic mechanisms, that was always going to be a forlorn hope.

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