Julia Pastrana was history's most famous bearded lady. In the 19th century, she fascinated spectators as part of a traveling circus, dancing and singing in clothes that showed off her hairy visage and limbs. In 1857, The Lancet documented Pastrana as a "peculiarity," but modern medicine shows that she suffered from a real disorder known as congenital generalized hypertrichosis terminalis (CGHT), sometimes called "werewolf syndrome." Now, Chinese scientists have begun to unravel the genetic story behind her condition.
CGHT is an extremely rare but highly heritable disorder. Scientists are unsure how many people have the condition, but there are at least 30 cases in China's billion-strong population. Affected men and women develop excessive dark hair across their bodies and faces. Some sufferers also have a broad, flat nose, large ears, a large mouth, and thick lips, and, occasionally, an enlarged head and jaw.
Hoping to discover the genetic basis of CGHT, geneticist Xue Zhang of the Peking Union Medical College in Beijing scoured his country for cases of the disease. After 4 years of searching through medical literature, the Internet, and even television, his team found three affected families, including 16 afflicted members willing to participate in the study. The researchers scanned the DNA of these individuals and compared it with the DNA of 19 family members without CGHT. After narrowing down the search to a short section on chromosome 17, the team looked for mutations called copy number variations, in which large chunks of DNA are repeated or removed. All of the CGHT sufferers had a copy number variation in which DNA was deleted across the same four genes, the authors report today in the American Journal of Human Genetics. None of the unaffected family members had the mutations.
Zhang speculates that the mutations change the local structure of the chromosome, interfering with the production of nearby genes. Indeed, one neighbor, SOX9, is linked to hair growth: Mice without it are known to suffer from hair loss, or alopecia. If the CGHT mutations somehow alter this region of chromosome 17 so that the SOX9 protein is overproduced in hair follicle stem cells, this would cause excessive hair growth, says Zhang. "But all this is pure speculation," he says.
Zhang may be onto something, says Eli Sprecher, a hair disorder expert at the Rappaport Institute in Haifa, Israel. Another hair-overgrowth condition-–Ambras syndrome--has been linked to chromosomal rearrangements, he notes, so it's plausible that CGHT works the same way. This study is "a first and important step" toward solving the puzzle of this disease, he says.