A new study led by researchers from University College London in the UK and the University of Milan in Italy has identified a genetic mutation that may be responsible for a condition that delays or prevents puberty, known as Kallmann syndrome.

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Researchers found a mutation in a gene called SEMA3E stops GnRH production, preventing puberty.

Kallmann syndrome is a rare inherited disorder estimated to affect around 1 in 10,000-86,000 people in the US, and it is more common among men. The condition is characterized by delayed onset or absence of puberty, alongside a reduced or diminished sense of smell.

Kallmann syndrome is caused by genetic mutations that interfere with gonadotropin-releasing hormone (GnRH). GnRH is released by nerve cells, or neurons, in the brain and is responsible for triggering puberty.

If diagnosed early enough, Kallmann syndrome can be treated with hormone injections. However, only around 40% of the genetic mutations responsible for the condition have been identified, meaning diagnosis is often delayed because it is hard to confirm its presence.

Now, study leader Dr. Anna Cariboni, of the Institute of Ophthalmology at University College London (UCL) and the Department of Pharmacological and Biomolecular Sciences at the University of Milan, and colleagues have identified another genetic mutation responsible for Kallmann syndrome, called SEMA3E.

What is more, the team has pinpointed exactly how the genetic mutation causes the condition.

Dr. Cariboni and colleagues reached their findings – recently published in The Journal of Clinical Investigation – by analyzing the blood samples of two brothers with Kallmann syndrome using a combination of exome sequencing and computational modeling.

From this, they identified a shared mutation in a gene called semaphorin 3E (SEMA3E) responsible for deficiency of GnRH in the two brothers.

By analyzing mouse models genetically modified to be absent of SEMA3E, and by recreating the SEMA3E mutation and testing it in nerve cells in tissue culture, the team found that SEMA3E normally protects the nerve cells responsible for regulating sexual reproduction. These nerve cells grow in the nose of developing fetuses before traveling to the brain to produce GnRH.

However, when SEMA3E is mutated, the nerve cells die during the journey from the nose to the brain, meaning GnRH is not produced and puberty does not occur.

The team says not only have their findings added to the list of genetic mutations known to cause Kallmann syndrome, they used techniques that could be employed to identify further mutations involved in the condition, as well as screen for such mutations.

The researchers add:

We have demonstrated that exome sequencing, combined with bioinformatics tools, tissue culture models, and the analysis of genetically modified mice, enables the identification and functional description of genes involved in GnRH neuron development and disease.

We therefore anticipate that our study will prompt direct SEMA3E mutation screening in Kallmann syndrome patients and lead to the increased application of exome sequencing for Kallmann syndrome gene discovery as well as provide a starting point for mechanistic studies of GnRH neuron development and deficiency.”

In July 2014, Medical News Today reported on a study of more than 180,000 women that found the age at which girls reach puberty may be influenced by a set of genes inherited from one parent.