ANOS1

Kallmann syndrome

More than 140 mutations in the ANOS1 gene have been identified in people with Kallmann syndrome, a disorder characterized by the combination of hypogonadotropic hypogonadism (a condition affecting the production of hormones that direct sexual development) and an impaired sense of smell. This condition can also affect other body systems, and its features vary among affected individuals. Researchers estimate that mutations in the ANOS1 gene account for 5 to 10 percent of all cases of Kallmann syndrome.

The ANOS1 gene mutations that cause Kallmann syndrome delete part or all of the gene, change single protein building blocks (amino acids) in anosmin-1, or alter the size of the protein. All of these mutations disrupt the normal production or function of anosmin-1 during embryonic development. Researchers suspect that the missing or altered protein is unable to direct the migration of olfactory nerve cells and GnRH-producing nerve cells to their usual locations in the developing brain. If olfactory nerve cells do not extend to the olfactory bulb, a person's sense of smell will be impaired. Misplacement of GnRH-producing neurons prevents the production of sex hormones, which interferes with normal sexual development and causes puberty to be delayed or absent.

It is unclear how ANOS1 gene mutations lead to other possible signs and symptoms of Kallmann syndrome, including a failure of one kidney to develop (unilateral renal agenesis), hearing loss, and mirror movements of the hands (bimanual synkinesia). Because these features vary among individuals, researchers suspect that other genetic and environmental factors may be involved. Some affected individuals have mutations in one of several other genes in addition to ANOS1, and these genetic changes may contribute to the varied features of the condition.