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Missing. Researchers have uncovered the mutation behind a rare disease that leaves people without fingerprints.

Nousbeck et al., The American Journal of Human Genetics (2011)

The Mystery of the Missing Fingerprints

In 2007, a Swiss woman in her late 20s had an unusually hard time crossing the U.S. border. Customs agents could not confirm her identity. The woman's passport picture matched her face just fine, but when the agents scanned her hands, they discovered something shocking: she had no fingerprints.

The woman, it turns out, had an extremely rare condition known as adermatoglyphia. Peter Itin, a dermatologist at the University Hospital Basel in Switzerland, has dubbed it the "immigration delay disease" because sufferers have such a hard time entering foreign countries. In addition to smooth fingertips, they also produce less hand sweat than the average person. Yet scientists know very little about what causes the condition.

Since nine members of the woman's extended family also lacked fingerprints, Itin and his colleagues, including Eli Sprecher, a dermatologist at the Tel Aviv Sourasky Medical Center in Israel, suspected that the cause might be genetic. So they collected DNA from the family—one of only four ever documented with ADG—and compared the genomes of family members with ADG with those of members who had normal fingerprints. The researchers found differences in 17 regions that were close to genes. Then they sequenced these genes, expecting to identify the culprit.

But the researchers didn't find anything. At first, Sprecher suspected that either they had performed the genetic analysis incorrectly or the missing mutation was hiding in a noncoding or "junk" region of the genome. "Then came the trick," he says. When graduate student Janna Nousbeck sifted through online databases of rare DNA transcripts that came from the suspect regions, she noticed one very short sequence that overlapped with part of a gene called SMARCAD1. This gene seemed like a likely candidate for the mutation since it was only expressed in the skin.

When the researchers sequenced SMARCAD1, their suspicions were confirmed: The gene was mutated in the fingerprintless family members, but not in the other family members. The mutation isn't in a region of the gene that codes for the SMARCAD1 protein; instead it's near a key splicing site that prevents SMARCAD1 from being made correctly, the researchers report today in The American Journal of Human Genetics.

Sprecher's next mission is to find out what exactly the function of SMARCAD1 is and how it contributes to the formation of fingerprint patterns, another unsolved mystery. But the researchers think that the gene might help skin cells fold over one another early in fetal development.

Terry Reed, a molecular geneticist at Indiana University School of Medicine in Indianapolis, who has also studied ADG, says that he is unsure whether SMARCAD1 is responsible for every patient who lacks fingerprints. He says he plans to sequence the gene from one of his own ADG patients. But he says that it's "gratifying to at least see a gene identified for this condition" and hopes it may help researchers understand skin development in general.

*A previous version of this story attributed the coining of the term "immigration delay disease" to Eli Sprecher. Credit instead belongs to Peter Itin. In addition, to clarify attribution, we have changed the text, "Sprecher and his colleagues suspected that the cause might be genetic," to "Itin and his colleagues, including Eli Sprecher, a dermatologist at the Tel Aviv Sourasky Medical Center in Israel, suspected that the cause might be genetic."