|Little Jimmy Scott was diagnosed with the rare disease|
Kallman Syndrome, preventing puberty. Now, new genetic
causes of the disease have been identified.
A molecule important in blood vessel formation and brain wiring is also essential for the onset of puberty, new research found. The researchers found a genetic fault that prevented this molecule, called SEMA3E, from working correctly in two brothers with Kallman Syndrome, an inherited condition that prevents people from undergoing puberty or being able to smell. They then studied mice without SEMA3E to see how its loss affected their development.
SEMA3E was found to protect the nerve cells that regulate sexual reproduction. These nerve cells grow in the nose of developing foetuses and then migrate to the brain where they produce gonadotropin releasing hormone (GnRH), which is needed to stimulate puberty. The research showed that these GnRH-producing nerve cells could not survive the migration without SEMA3E to protect them.
The new study, published in the Journal of Clinical Investigation, pinpointed genes responsible for Kallmann Syndrome in the two brothers and then verified the effect in tissue culture and mouse models. The cause of Kallmann Syndrome remains unknown in 60% of cases, so the techniques used in the study could be used to identify new genetic causes. The work also gives doctors a new confirmed genetic cause that patients could be tested for.
Kallmann Syndrome is a rare condition estimated to affect around 1 in 10,000 men and 1 in 50,000 women. It can be treated with hormone injections if diagnosed early enough, but it is difficult to confirm cases because only 40% of the genetic mutations that can cause it have been identified. The latest study not only adds to the known mutations that can be tested for, but also offers a new method to test 'unknown' cases in search of new mutations.
The study demonstrates a powerful method for identifying the causes of genetic conditions without relying on large statistical samples. This could be applied at clinical research centres studying many rare diseases, including Kallmann Syndrome, to identify mutations that people could be screened for.
Based on material originally posted by University College London.