CHD7

Mutations in the CHD7 gene cause CHARGE syndrome, a disorder that affects many areas of the body. CHARGE is an abbreviation for several of the features common in the disorder: coloboma, heart defect, atresia choanae (also known as choanal atresia), growth retardation, genital abnormality, and ear abnormality. More than 600 mutations that can cause CHARGE syndrome have been identified, and they occur throughout the CHD7 gene. Most of these mutations lead to the production of an abnormal CHD7 protein that is broken down prematurely. Shortage of this protein is thought to disrupt chromatin remodeling and the regulation of gene expression. Changes in gene expression during embryonic development likely cause the signs and symptoms of CHARGE syndrome.

More than 50 mutations in the CHD7 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. Mutations in this gene account for 5 to 10 percent of all cases of Kallmann syndrome.

Many people with Kallmann syndrome caused by a CHD7 gene mutation have some of the features of CHARGE syndrome (described above), such as abnormally shaped ears and hearing loss. However, the signs and symptoms tend to be much less severe. Researchers suspect that Kallmann syndrome resulting from a CHD7 gene mutation may actually represent a mild form of CHARGE syndrome.

Most of the CHD7 gene mutations that cause Kallmann syndrome alter single protein building blocks (amino acids) in the CHD7 protein. Studies suggest that these mutations have a less severe effect on protein function than those that cause CHARGE syndrome. The altered protein affects the development of the olfactory bulb, which impairs the sense of smell. It also disrupts the development of certain neurons needed for the production of sex hormones, which interferes with normal sexual development.

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