Hitting puberty isn't a particularly fun process at the best of times, but never going through it can be even worse. That's why researchers at University College London and the University of Milan were excited when they identified a molecule that appears to be imperative to kickstarting puberty.
Kallmann Syndrome is a rare condition that prevents people from experiencing puberty, or causes them to experience only partial puberty (it also causes them to have an impaired sense of smell). It is estimated to affect about 1 in every 10,000 men and 1 in every 50,000 women. It's treatable with hormone therapy, but only if it's caught early, which is tricky to do.
Doctors can screen for a set of genetic identifiers that are known to cause the condition, and if the patient has any of these genes then they can start treatment. But in 60 percent of the cases, these genes aren't the cause, making it difficult to determine if the patient has Kallmann Syndrome or is just a late bloomer.
To try to gain a better understanding of some of the other genetic factors that might lead to Kallmann Syndrome, researchers took at look at two brothers who both have the condition. They found that the semaphorin 3E (SEMA3E) protein wasn't working correctly in either brother, due to a genetic mutation. To see if there was any correlation, they observed mice who were born without the gene that tells SEMA3E what to do. It turns out, there was a correlation, as they explained in a paper published in the Journal of Clinical Investigation.
"We found concrete evidence showing how these mutations actually cause the condition," Christiana Ruhrberg, lead author of the study and a professor of Neuronal and Vascular Biology at UCL, said in a press release.
Ruhrberg and her colleagues found that SEMA3E protects nerve cells that help regulate sexual reproduction and produce gonadotropin releasing hormone (GnRH): hormones that jump start puberty. These nerve cells actually develop in our noses when we're still in the womb and as we get older, they migrate to the brain. But the study shows that, without SEMA3E to protect them, the cells die before they can ever tell the brain it's time for things to get hormone-y.
Ruhrberg said along with identifying yet another genetic cause for Kallmann Syndrome (broadening the list of indicators that doctors can screen for), the successful process helped create a new way of looking for genetic factors in rare diseases.
"By combining clinical and laboratory approaches, we were able to go far beyond simply identifying 'candidate' genes that might be linked to a given disease," she said. "Many genetic studies rely on statistical correlations from thousands of patients, making it difficult to study rare diseases such as Kallmann Syndrome. We managed to confirm genetic causes using blood samples from just two brothers with the condition, born two years apart."
Aside from good news in the effort to diagnose Kallmann Syndrome earlier, it's an exciting advancement for any researcher trying to pin down genetic influences in diseases that simply aren't that common. Turns out you don't need hundreds of patients to identify a gene—a couple of brothers will do.