A new study led by researchers from University College London (UK) and the University of Milan (Italy) has identified a genetic mutation that may be responsible for a medical condition that delays or prevents puberty, better known as Kallmann syndrome . The study has been published in The Journal of Clinical Investigation .
This inherited disorder is more common in men than in women. It affects the gonadotropin-releasing hormone (GnRH) of nerve cells or neurons in the brain and which is responsible for triggering puberty. Thus, people suffering from Kallmann syndrome, apart from having anosmia or loss of the sense of smell , also present – due to this lack of secretion of pituitary hormones that stimulate sex hormones (gonadotropins) – sexual deformation depending on the stage of development : as children, they present micropenis and cryptorchidism; in adolescence, incomplete sexual maturation and even hypogonadism and as an adult, a pre-pubertal testicular volume, erectile dysfunction, decreased libido and infertility.
The researchers analyzed blood samples from two siblings with Kallmann syndrome using a combination of exome sequencing – the coding parts of genes that will make up the mature messenger RNA – and computational modeling . Examination of these data allowed the identification of a new common genetic mutation called semaphorin 3E (Sema3E) that was responsible for GnRH deficiency in both study subjects.
After contrasting these results with experiments with mice genetically modified to avoid the presence of this mutation, they discovered that Sema3E protected the nerve cells responsible for the regulation of sexual reproduction that grow in the nose of developing fetuses before traveling to the brain. to produce GnRH. That is, the Sema3E mutation causes these nerve cells to die before reaching the brain, so puberty does not finally occur .
“We have shown that exome sequencing, combined with bioinformatics tools, tissue culture models and the analysis of genetically modified mice, allow the identification and description of the function of the genes involved in the development of GnRH neurons and the disease” explains Anna Cariboni, study leader.
