NSDHL

The NSDHL gene provides instructions for making an enzyme that is involved in the production (synthesis) of cholesterol. Cholesterol is a lipid (fat) that is obtained from foods that come from animals, particularly egg yolks, meat, fish, and dairy products. The body can also make (synthesize) its own cholesterol. During cholesterol synthesis, the NSDHL enzyme participates in one of several steps that convert a molecule called lanosterol to cholesterol. Specifically, the NSDHL enzyme removes a carbon atom and three hydrogen atoms (a methyl group) in the conversion of lanosterol to cholesterol.

Although high cholesterol levels are a well-known risk factor for heart disease, the body needs some cholesterol to develop and function normally. Before birth, cholesterol interacts with signaling proteins that control early development of the brain, limbs, genital tract, and other structures. It is also an important component of cell membranes and myelin, the fatty covering that insulates nerve cells. Additionally, cholesterol is used to make certain hormones and is important for the production of acids used in digestion (bile acids).

congenital hemidysplasia with ichthyosiform erythroderma and limb defects - caused by mutations in the NSDHL gene

At least 18 mutations in the NSDHL gene have been found to cause congenital hemidysplasia with ichthyosiform erythroderma and limb defects (CHILD syndrome). Most of these mutations change single protein building blocks (amino acids) in the NSDHL enzyme. A few other mutations delete part or all of the NSDHL gene. Each of the identified mutations likely prevents the production of any functional NSDHL enzyme, which disrupts the normal synthesis of cholesterol within cells. A shortage of this enzyme may also allow potentially toxic byproducts of cholesterol synthesis to build up in the body's tissues. Researchers suspect that low cholesterol levels and/or an accumulation of other substances disrupts the growth and development of many parts of the body. It is not known, however, how a disturbance in cholesterol synthesis leads to the specific features of CHILD syndrome.