Elephant Man Disease Caused by Single Gene That May be Treated, Study Says

(Corrects transposed letters in name of gene in seventh paragraph.)

Scientists say they have found a single gene mutation responsible for a rare condition thought to affect the disfigured “Elephant Man” who toured Europe in the 19th century and was the subject of a 1980 film.

Because the gene is also linked to cancer, drugs now in development may one day help similar patients, the researchers said. The disease, called the Proteus syndrome, is marked by uncontrolled tissue and bone growth. It’s named for the shape- shifting god from Greek mythology, and affects fewer than 500 people globally, according to the National Institutes of Health.

The single mutation, essentially one misspelling among 3 billion letters that comprise the human genome, occurs during fetal development and isn’t inherited, said Leslie Biesecker, the senior author of the report published today in the New England Journal of Medicine.

“All patients so far have exactly the same mutation in the same gene, and it’s never found in unaffected people,” said Biesecker, chief of genetic diseases research at the National Human Genome Research Institute, in a conference call with reporters. “Once the mutation happens, the cells that descend from that mutated cell display the uncontrolled growth that characterizes the disorder.”

Researchers said they plan to confirm the diagnosis of Joseph Merrick, who was played by John Hurt in the 1980 film, by analyzing his remains. Merrick died in 1890 in London.

The scientists found that the cells that were unaffected by the mutation continue to develop, giving the affected child two separate genomes. It’s difficult to for doctors to diagnose the condition because, in some cases, only the normal cells were studied, Biesecker said.

Gene Targeted

The mutation occurs in the AKT1 gene, which has been linked to tumors and may cause as much as 5 percent of breast cancers. Companies targeting AKT include GlaxoSmithKline Plc (GSK), Astra-Zeneca Plc, Zentaris Inc. and VioQuest Pharmaceuticals. Roche Holding AG (ROG)’s Tarceva and Eli Lilly & Co. (LLY)’s Erbitux appear to work, in part, by hitting AKT, studies have shown.

The researchers sequenced the part of the genome that codes proteins to pinpoint the mutation in seven patients with Proteus syndrome. They then tested 22 more patients, finding the mutation in 26 of the 29 tested. The other three may have the mutation at lower levels or in different tissues, the researchers said.

A subsequent analysis of 400 volunteers and thousands of others whose genomes are kept in public research databases failed to turn up the mutation in anyone without the condition.

15 Years of Tissue

The researchers did their analysis on tissue samples removed during surgery to control excessive bone and tissue growth during the past 15 years, said Eric Green, director of the National Human Genome Research Institute. The process took so long because they needed the technology to mature, he said.

“We are just starting to capitalize on the leading edge of this genomic revolution,” he said. “Like X-rays that peered into our bodies in the previous century, the power to routinely and robustly peer into our genomes will prove revolutionary,” he said.

To contact the reporter on this story: Michelle Fay Cortez in Minneapolis at mcortez@bloomberg.net

To contact the editor responsible for this story: Reg Gale at rgale5@bloomberg.net

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